how many articles for a research paper

• How to write a research paper

Last updated

11 January 2024

Reviewed by

With proper planning, knowledge, and framework, completing a research paper can be a fulfilling and exciting experience. 

Though it might initially sound slightly intimidating, this guide will help you embrace the challenge. 

By documenting your findings, you can inspire others and make a difference in your field. Here's how you can make your research paper unique and comprehensive.

• What is a research paper?

Research papers allow you to demonstrate your knowledge and understanding of a particular topic. These papers are usually lengthier and more detailed than typical essays, requiring deeper insight into the chosen topic.

To write a research paper, you must first choose a topic that interests you and is relevant to the field of study. Once you’ve selected your topic, gathering as many relevant resources as possible, including books, scholarly articles, credible websites, and other academic materials, is essential. You must then read and analyze these sources, summarizing their key points and identifying gaps in the current research.

You can formulate your ideas and opinions once you thoroughly understand the existing research. To get there might involve conducting original research, gathering data, or analyzing existing data sets. It could also involve presenting an original argument or interpretation of the existing research.

Writing a successful research paper involves presenting your findings clearly and engagingly, which might involve using charts, graphs, or other visual aids to present your data and using concise language to explain your findings. You must also ensure your paper adheres to relevant academic formatting guidelines, including proper citations and references.

Overall, writing a research paper requires a significant amount of time, effort, and attention to detail. However, it is also an enriching experience that allows you to delve deeply into a subject that interests you and contribute to the existing body of knowledge in your chosen field.

• How long should a research paper be?

Research papers are deep dives into a topic. Therefore, they tend to be longer pieces of work than essays or opinion pieces. 

However, a suitable length depends on the complexity of the topic and your level of expertise. For instance, are you a first-year college student or an experienced professional? 

Also, remember that the best research papers provide valuable information for the benefit of others. Therefore, the quality of information matters most, not necessarily the length. Being concise is valuable.

Following these best practice steps will help keep your process simple and productive:

1. Gaining a deep understanding of any expectations

Before diving into your intended topic or beginning the research phase, take some time to orient yourself. Suppose there’s a specific topic assigned to you. In that case, it’s essential to deeply understand the question and organize your planning and approach in response. Pay attention to the key requirements and ensure you align your writing accordingly. 

This preparation step entails

Deeply understanding the task or assignment

Being clear about the expected format and length

Familiarizing yourself with the citation and referencing requirements 

Understanding any defined limits for your research contribution

Where applicable, speaking to your professor or research supervisor for further clarification

2. Choose your research topic

Select a research topic that aligns with both your interests and available resources. Ideally, focus on a field where you possess significant experience and analytical skills. In crafting your research paper, it's crucial to go beyond summarizing existing data and contribute fresh insights to the chosen area.

Consider narrowing your focus to a specific aspect of the topic. For example, if exploring the link between technology and mental health, delve into how social media use during the pandemic impacts the well-being of college students. Conducting interviews and surveys with students could provide firsthand data and unique perspectives, adding substantial value to the existing knowledge.

When finalizing your topic, adhere to legal and ethical norms in the relevant area (this ensures the integrity of your research, protects participants' rights, upholds intellectual property standards, and ensures transparency and accountability). Following these principles not only maintains the credibility of your work but also builds trust within your academic or professional community.

For instance, in writing about medical research, consider legal and ethical norms , including patient confidentiality laws and informed consent requirements. Similarly, if analyzing user data on social media platforms, be mindful of data privacy regulations, ensuring compliance with laws governing personal information collection and use. Aligning with legal and ethical standards not only avoids potential issues but also underscores the responsible conduct of your research.

3. Gather preliminary research

Once you’ve landed on your topic, it’s time to explore it further. You’ll want to discover more about available resources and existing research relevant to your assignment at this stage. 

This exploratory phase is vital as you may discover issues with your original idea or realize you have insufficient resources to explore the topic effectively. This key bit of groundwork allows you to redirect your research topic in a different, more feasible, or more relevant direction if necessary. 

Spending ample time at this stage ensures you gather everything you need, learn as much as you can about the topic, and discover gaps where the topic has yet to be sufficiently covered, offering an opportunity to research it further. 

4. Define your research question

To produce a well-structured and focused paper, it is imperative to formulate a clear and precise research question that will guide your work. Your research question must be informed by the existing literature and tailored to the scope and objectives of your project. By refining your focus, you can produce a thoughtful and engaging paper that effectively communicates your ideas to your readers.

5. Write a thesis statement

A thesis statement is a one-to-two-sentence summary of your research paper's main argument or direction. It serves as an overall guide to summarize the overall intent of the research paper for you and anyone wanting to know more about the research.

A strong thesis statement is:

Concise and clear: Explain your case in simple sentences (avoid covering multiple ideas). It might help to think of this section as an elevator pitch.

Specific: Ensure that there is no ambiguity in your statement and that your summary covers the points argued in the paper.

Debatable: A thesis statement puts forward a specific argument––it is not merely a statement but a debatable point that can be analyzed and discussed.

Here are three thesis statement examples from different disciplines:

Psychology thesis example: "We're studying adults aged 25-40 to see if taking short breaks for mindfulness can help with stress. Our goal is to find practical ways to manage anxiety better."

Environmental science thesis example: "This research paper looks into how having more city parks might make the air cleaner and keep people healthier. I want to find out if more green spaces means breathing fewer carcinogens in big cities."

UX research thesis example: "This study focuses on improving mobile banking for older adults using ethnographic research, eye-tracking analysis, and interactive prototyping. We investigate the usefulness of eye-tracking analysis with older individuals, aiming to spark debate and offer fresh perspectives on UX design and digital inclusivity for the aging population."

6. Conduct in-depth research

A research paper doesn’t just include research that you’ve uncovered from other papers and studies but your fresh insights, too. You will seek to become an expert on your topic––understanding the nuances in the current leading theories. You will analyze existing research and add your thinking and discoveries.  It's crucial to conduct well-designed research that is rigorous, robust, and based on reliable sources. Suppose a research paper lacks evidence or is biased. In that case, it won't benefit the academic community or the general public. Therefore, examining the topic thoroughly and furthering its understanding through high-quality research is essential. That usually means conducting new research. Depending on the area under investigation, you may conduct surveys, interviews, diary studies , or observational research to uncover new insights or bolster current claims.

7. Determine supporting evidence

Not every piece of research you’ve discovered will be relevant to your research paper. It’s important to categorize the most meaningful evidence to include alongside your discoveries. It's important to include evidence that doesn't support your claims to avoid exclusion bias and ensure a fair research paper.

8. Write a research paper outline

Before diving in and writing the whole paper, start with an outline. It will help you to see if more research is needed, and it will provide a framework by which to write a more compelling paper. Your supervisor may even request an outline to approve before beginning to write the first draft of the full paper. An outline will include your topic, thesis statement, key headings, short summaries of the research, and your arguments.

9. Write your first draft

Once you feel confident about your outline and sources, it’s time to write your first draft. While penning a long piece of content can be intimidating, if you’ve laid the groundwork, you will have a structure to help you move steadily through each section. To keep up motivation and inspiration, it’s often best to keep the pace quick. Stopping for long periods can interrupt your flow and make jumping back in harder than writing when things are fresh in your mind.

10. Cite your sources correctly

It's always a good practice to give credit where it's due, and the same goes for citing any works that have influenced your paper. Building your arguments on credible references adds value and authenticity to your research. In the formatting guidelines section, you’ll find an overview of different citation styles (MLA, CMOS, or APA), which will help you meet any publishing or academic requirements and strengthen your paper's credibility. It is essential to follow the guidelines provided by your school or the publication you are submitting to ensure the accuracy and relevance of your citations.

11. Ensure your work is original

It is crucial to ensure the originality of your paper, as plagiarism can lead to serious consequences. To avoid plagiarism, you should use proper paraphrasing and quoting techniques. Paraphrasing is rewriting a text in your own words while maintaining the original meaning. Quoting involves directly citing the source. Giving credit to the original author or source is essential whenever you borrow their ideas or words. You can also use plagiarism detection tools such as Scribbr or Grammarly to check the originality of your paper. These tools compare your draft writing to a vast database of online sources. If you find any accidental plagiarism, you should correct it immediately by rephrasing or citing the source.

12. Revise, edit, and proofread

One of the essential qualities of excellent writers is their ability to understand the importance of editing and proofreading. Even though it's tempting to call it a day once you've finished your writing, editing your work can significantly improve its quality. It's natural to overlook the weaker areas when you've just finished writing a paper. Therefore, it's best to take a break of a day or two, or even up to a week, to refresh your mind. This way, you can return to your work with a new perspective. After some breathing room, you can spot any inconsistencies, spelling and grammar errors, typos, or missing citations and correct them. 

• The best research paper format 

The format of your research paper should align with the requirements set forth by your college, school, or target publication. 

There is no one “best” format, per se. Depending on the stated requirements, you may need to include the following elements:

Title page: The title page of a research paper typically includes the title, author's name, and institutional affiliation and may include additional information such as a course name or instructor's name. 

Table of contents: Include a table of contents to make it easy for readers to find specific sections of your paper.

Abstract: The abstract is a summary of the purpose of the paper.

Methods : In this section, describe the research methods used. This may include collecting data , conducting interviews, or doing field research .

Results: Summarize the conclusions you drew from your research in this section.

Discussion: In this section, discuss the implications of your research . Be sure to mention any significant limitations to your approach and suggest areas for further research.

Tables, charts, and illustrations: Use tables, charts, and illustrations to help convey your research findings and make them easier to understand.

Works cited or reference page: Include a works cited or reference page to give credit to the sources that you used to conduct your research.

Bibliography: Provide a list of all the sources you consulted while conducting your research.

Dedication and acknowledgments : Optionally, you may include a dedication and acknowledgments section to thank individuals who helped you with your research.

• General style and formatting guidelines

Formatting your research paper means you can submit it to your college, journal, or other publications in compliance with their criteria.

Research papers tend to follow the American Psychological Association (APA), Modern Language Association (MLA), or Chicago Manual of Style (CMOS) guidelines.

Here’s how each style guide is typically used:

Chicago Manual of Style (CMOS):

CMOS is a versatile style guide used for various types of writing. It's known for its flexibility and use in the humanities. CMOS provides guidelines for citations, formatting, and overall writing style. It allows for both footnotes and in-text citations, giving writers options based on their preferences or publication requirements.

American Psychological Association (APA):

APA is common in the social sciences. It’s hailed for its clarity and emphasis on precision. It has specific rules for citing sources, creating references, and formatting papers. APA style uses in-text citations with an accompanying reference list. It's designed to convey information efficiently and is widely used in academic and scientific writing.

Modern Language Association (MLA):

MLA is widely used in the humanities, especially literature and language studies. It emphasizes the author-page format for in-text citations and provides guidelines for creating a "Works Cited" page. MLA is known for its focus on the author's name and the literary works cited. It’s frequently used in disciplines that prioritize literary analysis and critical thinking.

To confirm you're using the latest style guide, check the official website or publisher's site for updates, consult academic resources, and verify the guide's publication date. Online platforms and educational resources may also provide summaries and alerts about any revisions or additions to the style guide.

Citing sources

When working on your research paper, it's important to cite the sources you used properly. Your citation style will guide you through this process. Generally, there are three parts to citing sources in your research paper: 

First, provide a brief citation in the body of your essay. This is also known as a parenthetical or in-text citation. 

Second, include a full citation in the Reference list at the end of your paper. Different types of citations include in-text citations, footnotes, and reference lists. 

In-text citations include the author's surname and the date of the citation. 

Footnotes appear at the bottom of each page of your research paper. They may also be summarized within a reference list at the end of the paper. 

A reference list includes all of the research used within the paper at the end of the document. It should include the author, date, paper title, and publisher listed in the order that aligns with your citation style.

10 research paper writing tips:

Following some best practices is essential to writing a research paper that contributes to your field of study and creates a positive impact.

These tactics will help you structure your argument effectively and ensure your work benefits others:

Clear and precise language:  Ensure your language is unambiguous. Use academic language appropriately, but keep it simple. Also, provide clear takeaways for your audience.

Effective idea separation:  Organize the vast amount of information and sources in your paper with paragraphs and titles. Create easily digestible sections for your readers to navigate through.

Compelling intro:  Craft an engaging introduction that captures your reader's interest. Hook your audience and motivate them to continue reading.

Thorough revision and editing:  Take the time to review and edit your paper comprehensively. Use tools like Grammarly to detect and correct small, overlooked errors.

Thesis precision:  Develop a clear and concise thesis statement that guides your paper. Ensure that your thesis aligns with your research's overall purpose and contribution.

Logical flow of ideas:  Maintain a logical progression throughout the paper. Use transitions effectively to connect different sections and maintain coherence.

Critical evaluation of sources:  Evaluate and critically assess the relevance and reliability of your sources. Ensure that your research is based on credible and up-to-date information.

Thematic consistency:  Maintain a consistent theme throughout the paper. Ensure that all sections contribute cohesively to the overall argument.

Relevant supporting evidence:  Provide concise and relevant evidence to support your arguments. Avoid unnecessary details that may distract from the main points.

Embrace counterarguments:  Acknowledge and address opposing views to strengthen your position. Show that you have considered alternative arguments in your field.

7 research tips 

If you want your paper to not only be well-written but also contribute to the progress of human knowledge, consider these tips to take your paper to the next level:

Selecting the appropriate topic: The topic you select should align with your area of expertise, comply with the requirements of your project, and have sufficient resources for a comprehensive investigation.

Use academic databases: Academic databases such as PubMed, Google Scholar, and JSTOR offer a wealth of research papers that can help you discover everything you need to know about your chosen topic.

Critically evaluate sources: It is important not to accept research findings at face value. Instead, it is crucial to critically analyze the information to avoid jumping to conclusions or overlooking important details. A well-written research paper requires a critical analysis with thorough reasoning to support claims.

Diversify your sources: Expand your research horizons by exploring a variety of sources beyond the standard databases. Utilize books, conference proceedings, and interviews to gather diverse perspectives and enrich your understanding of the topic.

Take detailed notes: Detailed note-taking is crucial during research and can help you form the outline and body of your paper.

Stay up on trends: Keep abreast of the latest developments in your field by regularly checking for recent publications. Subscribe to newsletters, follow relevant journals, and attend conferences to stay informed about emerging trends and advancements. 

Engage in peer review: Seek feedback from peers or mentors to ensure the rigor and validity of your research . Peer review helps identify potential weaknesses in your methodology and strengthens the overall credibility of your findings.

• The real-world impact of research papers

Writing a research paper is more than an academic or business exercise. The experience provides an opportunity to explore a subject in-depth, broaden one's understanding, and arrive at meaningful conclusions. With careful planning, dedication, and hard work, writing a research paper can be a fulfilling and enriching experience contributing to advancing knowledge.

How do I publish my research paper? 

Many academics wish to publish their research papers. While challenging, your paper might get traction if it covers new and well-written information. To publish your research paper, find a target publication, thoroughly read their guidelines, format your paper accordingly, and send it to them per their instructions. You may need to include a cover letter, too. After submission, your paper may be peer-reviewed by experts to assess its legitimacy, quality, originality, and methodology. Following review, you will be informed by the publication whether they have accepted or rejected your paper. 

What is a good opening sentence for a research paper? 

Beginning your research paper with a compelling introduction can ensure readers are interested in going further. A relevant quote, a compelling statistic, or a bold argument can start the paper and hook your reader. Remember, though, that the most important aspect of a research paper is the quality of the information––not necessarily your ability to storytell, so ensure anything you write aligns with your goals.

Research paper vs. a research proposal—what’s the difference?

While some may confuse research papers and proposals, they are different documents. 

A research proposal comes before a research paper. It is a detailed document that outlines an intended area of exploration. It includes the research topic, methodology, timeline, sources, and potential conclusions. Research proposals are often required when seeking approval to conduct research. 

A research paper is a summary of research findings. A research paper follows a structured format to present those findings and construct an argument or conclusion.

Should you be using a customer insights hub?

Do you want to discover previous research faster?

Do you share your research findings with others?

Do you analyze research data?

Start for free today, add your research, and get to key insights faster

Editor’s picks

Last updated: 18 April 2023

Last updated: 27 February 2023

Last updated: 5 February 2023

Last updated: 16 April 2023

Last updated: 16 August 2024

Last updated: 9 March 2023

Last updated: 30 April 2024

Last updated: 12 December 2023

Last updated: 11 March 2024

Last updated: 4 July 2024

Last updated: 6 March 2024

Last updated: 5 March 2024

Last updated: 13 May 2024

Latest articles

Related topics, .css-je19u9{-webkit-align-items:flex-end;-webkit-box-align:flex-end;-ms-flex-align:flex-end;align-items:flex-end;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:row;-ms-flex-direction:row;flex-direction:row;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-box-pack:center;-ms-flex-pack:center;-webkit-justify-content:center;justify-content:center;row-gap:0;text-align:center;max-width:671px;}@media (max-width: 1079px){.css-je19u9{max-width:400px;}.css-je19u9>span{white-space:pre;}}@media (max-width: 799px){.css-je19u9{max-width:400px;}.css-je19u9>span{white-space:pre;}} decide what to .css-1kiodld{max-height:56px;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}@media (max-width: 1079px){.css-1kiodld{display:none;}} build next, decide what to build next.

• 10 research paper

Log in or sign up

Get started for free

• Search Menu
• Sign in through your institution
• Advance articles
• Editor's Choice
• Supplements
• French Abstracts
• Portuguese Abstracts
• Spanish Abstracts
• Author Guidelines
• Submission Site
• Open Access
• About International Journal for Quality in Health Care
• About the International Society for Quality in Health Care
• Editorial Board
• Advertising and Corporate Services
• Journals Career Network
• Self-Archiving Policy
• Dispatch Dates
• Contact ISQua
• Journals on Oxford Academic
• Books on Oxford Academic

Article Contents

Primacy of the research question, structure of the paper, writing a research article: advice to beginners.

• Article contents
• Figures & tables
• Supplementary Data

Thomas V. Perneger, Patricia M. Hudelson, Writing a research article: advice to beginners, International Journal for Quality in Health Care , Volume 16, Issue 3, June 2004, Pages 191–192, https://doi.org/10.1093/intqhc/mzh053

• Permissions Icon Permissions

Writing research papers does not come naturally to most of us. The typical research paper is a highly codified rhetorical form [ 1 , 2 ]. Knowledge of the rules—some explicit, others implied—goes a long way toward writing a paper that will get accepted in a peer-reviewed journal.

A good research paper addresses a specific research question. The research question—or study objective or main research hypothesis—is the central organizing principle of the paper. Whatever relates to the research question belongs in the paper; the rest doesn’t. This is perhaps obvious when the paper reports on a well planned research project. However, in applied domains such as quality improvement, some papers are written based on projects that were undertaken for operational reasons, and not with the primary aim of producing new knowledge. In such cases, authors should define the main research question a posteriori and design the paper around it.

Generally, only one main research question should be addressed in a paper (secondary but related questions are allowed). If a project allows you to explore several distinct research questions, write several papers. For instance, if you measured the impact of obtaining written consent on patient satisfaction at a specialized clinic using a newly developed questionnaire, you may want to write one paper on the questionnaire development and validation, and another on the impact of the intervention. The idea is not to split results into ‘least publishable units’, a practice that is rightly decried, but rather into ‘optimally publishable units’.

What is a good research question? The key attributes are: (i) specificity; (ii) originality or novelty; and (iii) general relevance to a broad scientific community. The research question should be precise and not merely identify a general area of inquiry. It can often (but not always) be expressed in terms of a possible association between X and Y in a population Z, for example ‘we examined whether providing patients about to be discharged from the hospital with written information about their medications would improve their compliance with the treatment 1 month later’. A study does not necessarily have to break completely new ground, but it should extend previous knowledge in a useful way, or alternatively refute existing knowledge. Finally, the question should be of interest to others who work in the same scientific area. The latter requirement is more challenging for those who work in applied science than for basic scientists. While it may safely be assumed that the human genome is the same worldwide, whether the results of a local quality improvement project have wider relevance requires careful consideration and argument.

Once the research question is clearly defined, writing the paper becomes considerably easier. The paper will ask the question, then answer it. The key to successful scientific writing is getting the structure of the paper right. The basic structure of a typical research paper is the sequence of Introduction, Methods, Results, and Discussion (sometimes abbreviated as IMRAD). Each section addresses a different objective. The authors state: (i) the problem they intend to address—in other terms, the research question—in the Introduction; (ii) what they did to answer the question in the Methods section; (iii) what they observed in the Results section; and (iv) what they think the results mean in the Discussion.

In turn, each basic section addresses several topics, and may be divided into subsections (Table 1 ). In the Introduction, the authors should explain the rationale and background to the study. What is the research question, and why is it important to ask it? While it is neither necessary nor desirable to provide a full-blown review of the literature as a prelude to the study, it is helpful to situate the study within some larger field of enquiry. The research question should always be spelled out, and not merely left for the reader to guess.

Typical structure of a research paper

The Methods section should provide the readers with sufficient detail about the study methods to be able to reproduce the study if so desired. Thus, this section should be specific, concrete, technical, and fairly detailed. The study setting, the sampling strategy used, instruments, data collection methods, and analysis strategies should be described. In the case of qualitative research studies, it is also useful to tell the reader which research tradition the study utilizes and to link the choice of methodological strategies with the research goals [ 3 ].

The Results section is typically fairly straightforward and factual. All results that relate to the research question should be given in detail, including simple counts and percentages. Resist the temptation to demonstrate analytic ability and the richness of the dataset by providing numerous tables of non-essential results.

The Discussion section allows the most freedom. This is why the Discussion is the most difficult to write, and is often the weakest part of a paper. Structured Discussion sections have been proposed by some journal editors [ 4 ]. While strict adherence to such rules may not be necessary, following a plan such as that proposed in Table 1 may help the novice writer stay on track.

References should be used wisely. Key assertions should be referenced, as well as the methods and instruments used. However, unless the paper is a comprehensive review of a topic, there is no need to be exhaustive. Also, references to unpublished work, to documents in the grey literature (technical reports), or to any source that the reader will have difficulty finding or understanding should be avoided.

Having the structure of the paper in place is a good start. However, there are many details that have to be attended to while writing. An obvious recommendation is to read, and follow, the instructions to authors published by the journal (typically found on the journal’s website). Another concerns non-native writers of English: do have a native speaker edit the manuscript. A paper usually goes through several drafts before it is submitted. When revising a paper, it is useful to keep an eye out for the most common mistakes (Table 2 ). If you avoid all those, your paper should be in good shape.

Common mistakes seen in manuscripts submitted to this journal

Huth EJ . How to Write and Publish Papers in the Medical Sciences , 2nd edition. Baltimore, MD: Williams & Wilkins, 1990 .

Browner WS . Publishing and Presenting Clinical Research . Baltimore, MD: Lippincott, Williams & Wilkins, 1999 .

Devers KJ , Frankel RM. Getting qualitative research published. Educ Health 2001 ; 14 : 109 –117.

Docherty M , Smith R. The case for structuring the discussion of scientific papers. Br Med J 1999 ; 318 : 1224 –1225.

Email alerts

Citing articles via.

• Recommend to your Library

Affiliations

• Online ISSN 1464-3677
• Print ISSN 1353-4505
• Copyright © 2024 International Society for Quality in Health Care and Oxford University Press
• About Oxford Academic
• Publish journals with us
• University press partners
• What we publish
• New features  
• Open access
• Institutional account management
• Rights and permissions
• Get help with access
• Accessibility
• Advertising
• Media enquiries
• Oxford University Press
• Oxford Languages
• University of Oxford

Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide

• Copyright © 2024 Oxford University Press
• Cookie settings
• Cookie policy
• Privacy policy
• Legal notice

This Feature Is Available To Subscribers Only

Sign In or Create an Account

This PDF is available to Subscribers Only

For full access to this pdf, sign in to an existing account, or purchase an annual subscription.

• Privacy Policy

Home » Research Paper – Structure, Examples and Writing Guide

Research Paper – Structure, Examples and Writing Guide

Table of Contents

Research Paper

Definition:

Research Paper is a written document that presents the author’s original research, analysis, and interpretation of a specific topic or issue.

It is typically based on Empirical Evidence, and may involve qualitative or quantitative research methods, or a combination of both. The purpose of a research paper is to contribute new knowledge or insights to a particular field of study, and to demonstrate the author’s understanding of the existing literature and theories related to the topic.

Structure of Research Paper

The structure of a research paper typically follows a standard format, consisting of several sections that convey specific information about the research study. The following is a detailed explanation of the structure of a research paper:

The title page contains the title of the paper, the name(s) of the author(s), and the affiliation(s) of the author(s). It also includes the date of submission and possibly, the name of the journal or conference where the paper is to be published.

The abstract is a brief summary of the research paper, typically ranging from 100 to 250 words. It should include the research question, the methods used, the key findings, and the implications of the results. The abstract should be written in a concise and clear manner to allow readers to quickly grasp the essence of the research.

Introduction

The introduction section of a research paper provides background information about the research problem, the research question, and the research objectives. It also outlines the significance of the research, the research gap that it aims to fill, and the approach taken to address the research question. Finally, the introduction section ends with a clear statement of the research hypothesis or research question.

Literature Review

The literature review section of a research paper provides an overview of the existing literature on the topic of study. It includes a critical analysis and synthesis of the literature, highlighting the key concepts, themes, and debates. The literature review should also demonstrate the research gap and how the current study seeks to address it.

The methods section of a research paper describes the research design, the sample selection, the data collection and analysis procedures, and the statistical methods used to analyze the data. This section should provide sufficient detail for other researchers to replicate the study.

The results section presents the findings of the research, using tables, graphs, and figures to illustrate the data. The findings should be presented in a clear and concise manner, with reference to the research question and hypothesis.

The discussion section of a research paper interprets the findings and discusses their implications for the research question, the literature review, and the field of study. It should also address the limitations of the study and suggest future research directions.

The conclusion section summarizes the main findings of the study, restates the research question and hypothesis, and provides a final reflection on the significance of the research.

The references section provides a list of all the sources cited in the paper, following a specific citation style such as APA, MLA or Chicago.

How to Write Research Paper

You can write Research Paper by the following guide:

• Choose a Topic: The first step is to select a topic that interests you and is relevant to your field of study. Brainstorm ideas and narrow down to a research question that is specific and researchable.
• Conduct a Literature Review: The literature review helps you identify the gap in the existing research and provides a basis for your research question. It also helps you to develop a theoretical framework and research hypothesis.
• Develop a Thesis Statement : The thesis statement is the main argument of your research paper. It should be clear, concise and specific to your research question.
• Plan your Research: Develop a research plan that outlines the methods, data sources, and data analysis procedures. This will help you to collect and analyze data effectively.
• Collect and Analyze Data: Collect data using various methods such as surveys, interviews, observations, or experiments. Analyze data using statistical tools or other qualitative methods.
• Organize your Paper : Organize your paper into sections such as Introduction, Literature Review, Methods, Results, Discussion, and Conclusion. Ensure that each section is coherent and follows a logical flow.
• Write your Paper : Start by writing the introduction, followed by the literature review, methods, results, discussion, and conclusion. Ensure that your writing is clear, concise, and follows the required formatting and citation styles.
• Edit and Proofread your Paper: Review your paper for grammar and spelling errors, and ensure that it is well-structured and easy to read. Ask someone else to review your paper to get feedback and suggestions for improvement.
• Cite your Sources: Ensure that you properly cite all sources used in your research paper. This is essential for giving credit to the original authors and avoiding plagiarism.

Research Paper Example

Note : The below example research paper is for illustrative purposes only and is not an actual research paper. Actual research papers may have different structures, contents, and formats depending on the field of study, research question, data collection and analysis methods, and other factors. Students should always consult with their professors or supervisors for specific guidelines and expectations for their research papers.

Research Paper Example sample for Students:

Title: The Impact of Social Media on Mental Health among Young Adults

Abstract: This study aims to investigate the impact of social media use on the mental health of young adults. A literature review was conducted to examine the existing research on the topic. A survey was then administered to 200 university students to collect data on their social media use, mental health status, and perceived impact of social media on their mental health. The results showed that social media use is positively associated with depression, anxiety, and stress. The study also found that social comparison, cyberbullying, and FOMO (Fear of Missing Out) are significant predictors of mental health problems among young adults.

Introduction: Social media has become an integral part of modern life, particularly among young adults. While social media has many benefits, including increased communication and social connectivity, it has also been associated with negative outcomes, such as addiction, cyberbullying, and mental health problems. This study aims to investigate the impact of social media use on the mental health of young adults.

Literature Review: The literature review highlights the existing research on the impact of social media use on mental health. The review shows that social media use is associated with depression, anxiety, stress, and other mental health problems. The review also identifies the factors that contribute to the negative impact of social media, including social comparison, cyberbullying, and FOMO.

Methods : A survey was administered to 200 university students to collect data on their social media use, mental health status, and perceived impact of social media on their mental health. The survey included questions on social media use, mental health status (measured using the DASS-21), and perceived impact of social media on their mental health. Data were analyzed using descriptive statistics and regression analysis.

Results : The results showed that social media use is positively associated with depression, anxiety, and stress. The study also found that social comparison, cyberbullying, and FOMO are significant predictors of mental health problems among young adults.

Discussion : The study’s findings suggest that social media use has a negative impact on the mental health of young adults. The study highlights the need for interventions that address the factors contributing to the negative impact of social media, such as social comparison, cyberbullying, and FOMO.

Conclusion : In conclusion, social media use has a significant impact on the mental health of young adults. The study’s findings underscore the need for interventions that promote healthy social media use and address the negative outcomes associated with social media use. Future research can explore the effectiveness of interventions aimed at reducing the negative impact of social media on mental health. Additionally, longitudinal studies can investigate the long-term effects of social media use on mental health.

Limitations : The study has some limitations, including the use of self-report measures and a cross-sectional design. The use of self-report measures may result in biased responses, and a cross-sectional design limits the ability to establish causality.

Implications: The study’s findings have implications for mental health professionals, educators, and policymakers. Mental health professionals can use the findings to develop interventions that address the negative impact of social media use on mental health. Educators can incorporate social media literacy into their curriculum to promote healthy social media use among young adults. Policymakers can use the findings to develop policies that protect young adults from the negative outcomes associated with social media use.

References :

• Twenge, J. M., & Campbell, W. K. (2019). Associations between screen time and lower psychological well-being among children and adolescents: Evidence from a population-based study. Preventive medicine reports, 15, 100918.
• Primack, B. A., Shensa, A., Escobar-Viera, C. G., Barrett, E. L., Sidani, J. E., Colditz, J. B., … & James, A. E. (2017). Use of multiple social media platforms and symptoms of depression and anxiety: A nationally-representative study among US young adults. Computers in Human Behavior, 69, 1-9.
• Van der Meer, T. G., & Verhoeven, J. W. (2017). Social media and its impact on academic performance of students. Journal of Information Technology Education: Research, 16, 383-398.

Appendix : The survey used in this study is provided below.

Social Media and Mental Health Survey

• How often do you use social media per day?
• Less than 30 minutes
• 30 minutes to 1 hour
• 1 to 2 hours
• 2 to 4 hours
• More than 4 hours
• Which social media platforms do you use?
• Others (Please specify)
• How often do you experience the following on social media?
• Social comparison (comparing yourself to others)
• Cyberbullying
• Fear of Missing Out (FOMO)
• Have you ever experienced any of the following mental health problems in the past month?
• Do you think social media use has a positive or negative impact on your mental health?
• Very positive
• Somewhat positive
• Somewhat negative
• Very negative
• In your opinion, which factors contribute to the negative impact of social media on mental health?
• Social comparison
• In your opinion, what interventions could be effective in reducing the negative impact of social media on mental health?
• Education on healthy social media use
• Counseling for mental health problems caused by social media
• Social media detox programs
• Regulation of social media use

Thank you for your participation!

Applications of Research Paper

Research papers have several applications in various fields, including:

• Advancing knowledge: Research papers contribute to the advancement of knowledge by generating new insights, theories, and findings that can inform future research and practice. They help to answer important questions, clarify existing knowledge, and identify areas that require further investigation.
• Informing policy: Research papers can inform policy decisions by providing evidence-based recommendations for policymakers. They can help to identify gaps in current policies, evaluate the effectiveness of interventions, and inform the development of new policies and regulations.
• Improving practice: Research papers can improve practice by providing evidence-based guidance for professionals in various fields, including medicine, education, business, and psychology. They can inform the development of best practices, guidelines, and standards of care that can improve outcomes for individuals and organizations.
• Educating students : Research papers are often used as teaching tools in universities and colleges to educate students about research methods, data analysis, and academic writing. They help students to develop critical thinking skills, research skills, and communication skills that are essential for success in many careers.
• Fostering collaboration: Research papers can foster collaboration among researchers, practitioners, and policymakers by providing a platform for sharing knowledge and ideas. They can facilitate interdisciplinary collaborations and partnerships that can lead to innovative solutions to complex problems.

When to Write Research Paper

Research papers are typically written when a person has completed a research project or when they have conducted a study and have obtained data or findings that they want to share with the academic or professional community. Research papers are usually written in academic settings, such as universities, but they can also be written in professional settings, such as research organizations, government agencies, or private companies.

Here are some common situations where a person might need to write a research paper:

• For academic purposes: Students in universities and colleges are often required to write research papers as part of their coursework, particularly in the social sciences, natural sciences, and humanities. Writing research papers helps students to develop research skills, critical thinking skills, and academic writing skills.
• For publication: Researchers often write research papers to publish their findings in academic journals or to present their work at academic conferences. Publishing research papers is an important way to disseminate research findings to the academic community and to establish oneself as an expert in a particular field.
• To inform policy or practice : Researchers may write research papers to inform policy decisions or to improve practice in various fields. Research findings can be used to inform the development of policies, guidelines, and best practices that can improve outcomes for individuals and organizations.
• To share new insights or ideas: Researchers may write research papers to share new insights or ideas with the academic or professional community. They may present new theories, propose new research methods, or challenge existing paradigms in their field.

Purpose of Research Paper

The purpose of a research paper is to present the results of a study or investigation in a clear, concise, and structured manner. Research papers are written to communicate new knowledge, ideas, or findings to a specific audience, such as researchers, scholars, practitioners, or policymakers. The primary purposes of a research paper are:

• To contribute to the body of knowledge : Research papers aim to add new knowledge or insights to a particular field or discipline. They do this by reporting the results of empirical studies, reviewing and synthesizing existing literature, proposing new theories, or providing new perspectives on a topic.
• To inform or persuade: Research papers are written to inform or persuade the reader about a particular issue, topic, or phenomenon. They present evidence and arguments to support their claims and seek to persuade the reader of the validity of their findings or recommendations.
• To advance the field: Research papers seek to advance the field or discipline by identifying gaps in knowledge, proposing new research questions or approaches, or challenging existing assumptions or paradigms. They aim to contribute to ongoing debates and discussions within a field and to stimulate further research and inquiry.
• To demonstrate research skills: Research papers demonstrate the author’s research skills, including their ability to design and conduct a study, collect and analyze data, and interpret and communicate findings. They also demonstrate the author’s ability to critically evaluate existing literature, synthesize information from multiple sources, and write in a clear and structured manner.

Characteristics of Research Paper

Research papers have several characteristics that distinguish them from other forms of academic or professional writing. Here are some common characteristics of research papers:

• Evidence-based: Research papers are based on empirical evidence, which is collected through rigorous research methods such as experiments, surveys, observations, or interviews. They rely on objective data and facts to support their claims and conclusions.
• Structured and organized: Research papers have a clear and logical structure, with sections such as introduction, literature review, methods, results, discussion, and conclusion. They are organized in a way that helps the reader to follow the argument and understand the findings.
• Formal and objective: Research papers are written in a formal and objective tone, with an emphasis on clarity, precision, and accuracy. They avoid subjective language or personal opinions and instead rely on objective data and analysis to support their arguments.
• Citations and references: Research papers include citations and references to acknowledge the sources of information and ideas used in the paper. They use a specific citation style, such as APA, MLA, or Chicago, to ensure consistency and accuracy.
• Peer-reviewed: Research papers are often peer-reviewed, which means they are evaluated by other experts in the field before they are published. Peer-review ensures that the research is of high quality, meets ethical standards, and contributes to the advancement of knowledge in the field.
• Objective and unbiased: Research papers strive to be objective and unbiased in their presentation of the findings. They avoid personal biases or preconceptions and instead rely on the data and analysis to draw conclusions.

Advantages of Research Paper

Research papers have many advantages, both for the individual researcher and for the broader academic and professional community. Here are some advantages of research papers:

• Contribution to knowledge: Research papers contribute to the body of knowledge in a particular field or discipline. They add new information, insights, and perspectives to existing literature and help advance the understanding of a particular phenomenon or issue.
• Opportunity for intellectual growth: Research papers provide an opportunity for intellectual growth for the researcher. They require critical thinking, problem-solving, and creativity, which can help develop the researcher’s skills and knowledge.
• Career advancement: Research papers can help advance the researcher’s career by demonstrating their expertise and contributions to the field. They can also lead to new research opportunities, collaborations, and funding.
• Academic recognition: Research papers can lead to academic recognition in the form of awards, grants, or invitations to speak at conferences or events. They can also contribute to the researcher’s reputation and standing in the field.
• Impact on policy and practice: Research papers can have a significant impact on policy and practice. They can inform policy decisions, guide practice, and lead to changes in laws, regulations, or procedures.
• Advancement of society: Research papers can contribute to the advancement of society by addressing important issues, identifying solutions to problems, and promoting social justice and equality.

Limitations of Research Paper

Research papers also have some limitations that should be considered when interpreting their findings or implications. Here are some common limitations of research papers:

• Limited generalizability: Research findings may not be generalizable to other populations, settings, or contexts. Studies often use specific samples or conditions that may not reflect the broader population or real-world situations.
• Potential for bias : Research papers may be biased due to factors such as sample selection, measurement errors, or researcher biases. It is important to evaluate the quality of the research design and methods used to ensure that the findings are valid and reliable.
• Ethical concerns: Research papers may raise ethical concerns, such as the use of vulnerable populations or invasive procedures. Researchers must adhere to ethical guidelines and obtain informed consent from participants to ensure that the research is conducted in a responsible and respectful manner.
• Limitations of methodology: Research papers may be limited by the methodology used to collect and analyze data. For example, certain research methods may not capture the complexity or nuance of a particular phenomenon, or may not be appropriate for certain research questions.
• Publication bias: Research papers may be subject to publication bias, where positive or significant findings are more likely to be published than negative or non-significant findings. This can skew the overall findings of a particular area of research.
• Time and resource constraints: Research papers may be limited by time and resource constraints, which can affect the quality and scope of the research. Researchers may not have access to certain data or resources, or may be unable to conduct long-term studies due to practical limitations.

About the author

Muhammad Hassan

Researcher, Academic Writer, Web developer

You may also like

Research Paper Outline – Types, Example, Template

Research Paper Conclusion – Writing Guide and...

Implications in Research – Types, Examples and...

Table of Contents – Types, Formats, Examples

Research Methods – Types, Examples and Guide

Research Paper Title Page – Example and Making...

How to Write and Publish a Research Paper for a Peer-Reviewed Journal

• Open access
• Published: 30 April 2020
• Volume 36 , pages 909–913, ( 2021 )

Cite this article

You have full access to this open access article

• Clara Busse   ORCID: orcid.org/0000-0002-0178-1000 1 &
• Ella August   ORCID: orcid.org/0000-0001-5151-1036 1 , 2  

280k Accesses

15 Citations

710 Altmetric

Explore all metrics

Communicating research findings is an essential step in the research process. Often, peer-reviewed journals are the forum for such communication, yet many researchers are never taught how to write a publishable scientific paper. In this article, we explain the basic structure of a scientific paper and describe the information that should be included in each section. We also identify common pitfalls for each section and recommend strategies to avoid them. Further, we give advice about target journal selection and authorship. In the online resource 1 , we provide an example of a high-quality scientific paper, with annotations identifying the elements we describe in this article.

Similar content being viewed by others

How to Choose the Right Journal

The Point Is…to Publish?

Writing and publishing a scientific paper

Explore related subjects.

• Artificial Intelligence

Avoid common mistakes on your manuscript.

Introduction

Writing a scientific paper is an important component of the research process, yet researchers often receive little formal training in scientific writing. This is especially true in low-resource settings. In this article, we explain why choosing a target journal is important, give advice about authorship, provide a basic structure for writing each section of a scientific paper, and describe common pitfalls and recommendations for each section. In the online resource 1 , we also include an annotated journal article that identifies the key elements and writing approaches that we detail here. Before you begin your research, make sure you have ethical clearance from all relevant ethical review boards.

Select a Target Journal Early in the Writing Process

We recommend that you select a “target journal” early in the writing process; a “target journal” is the journal to which you plan to submit your paper. Each journal has a set of core readers and you should tailor your writing to this readership. For example, if you plan to submit a manuscript about vaping during pregnancy to a pregnancy-focused journal, you will need to explain what vaping is because readers of this journal may not have a background in this topic. However, if you were to submit that same article to a tobacco journal, you would not need to provide as much background information about vaping.

Information about a journal’s core readership can be found on its website, usually in a section called “About this journal” or something similar. For example, the Journal of Cancer Education presents such information on the “Aims and Scope” page of its website, which can be found here: https://www.springer.com/journal/13187/aims-and-scope .

Peer reviewer guidelines from your target journal are an additional resource that can help you tailor your writing to the journal and provide additional advice about crafting an effective article [ 1 ]. These are not always available, but it is worth a quick web search to find out.

Identify Author Roles Early in the Process

Early in the writing process, identify authors, determine the order of authors, and discuss the responsibilities of each author. Standard author responsibilities have been identified by The International Committee of Medical Journal Editors (ICMJE) [ 2 ]. To set clear expectations about each team member’s responsibilities and prevent errors in communication, we also suggest outlining more detailed roles, such as who will draft each section of the manuscript, write the abstract, submit the paper electronically, serve as corresponding author, and write the cover letter. It is best to formalize this agreement in writing after discussing it, circulating the document to the author team for approval. We suggest creating a title page on which all authors are listed in the agreed-upon order. It may be necessary to adjust authorship roles and order during the development of the paper. If a new author order is agreed upon, be sure to update the title page in the manuscript draft.

In the case where multiple papers will result from a single study, authors should discuss who will author each paper. Additionally, authors should agree on a deadline for each paper and the lead author should take responsibility for producing an initial draft by this deadline.

Structure of the Introduction Section

The introduction section should be approximately three to five paragraphs in length. Look at examples from your target journal to decide the appropriate length. This section should include the elements shown in Fig.  1 . Begin with a general context, narrowing to the specific focus of the paper. Include five main elements: why your research is important, what is already known about the topic, the “gap” or what is not yet known about the topic, why it is important to learn the new information that your research adds, and the specific research aim(s) that your paper addresses. Your research aim should address the gap you identified. Be sure to add enough background information to enable readers to understand your study. Table 1 provides common introduction section pitfalls and recommendations for addressing them.

The main elements of the introduction section of an original research article. Often, the elements overlap

Methods Section

The purpose of the methods section is twofold: to explain how the study was done in enough detail to enable its replication and to provide enough contextual detail to enable readers to understand and interpret the results. In general, the essential elements of a methods section are the following: a description of the setting and participants, the study design and timing, the recruitment and sampling, the data collection process, the dataset, the dependent and independent variables, the covariates, the analytic approach for each research objective, and the ethical approval. The hallmark of an exemplary methods section is the justification of why each method was used. Table 2 provides common methods section pitfalls and recommendations for addressing them.

Results Section

The focus of the results section should be associations, or lack thereof, rather than statistical tests. Two considerations should guide your writing here. First, the results should present answers to each part of the research aim. Second, return to the methods section to ensure that the analysis and variables for each result have been explained.

Begin the results section by describing the number of participants in the final sample and details such as the number who were approached to participate, the proportion who were eligible and who enrolled, and the number of participants who dropped out. The next part of the results should describe the participant characteristics. After that, you may organize your results by the aim or by putting the most exciting results first. Do not forget to report your non-significant associations. These are still findings.

Tables and figures capture the reader’s attention and efficiently communicate your main findings [ 3 ]. Each table and figure should have a clear message and should complement, rather than repeat, the text. Tables and figures should communicate all salient details necessary for a reader to understand the findings without consulting the text. Include information on comparisons and tests, as well as information about the sample and timing of the study in the title, legend, or in a footnote. Note that figures are often more visually interesting than tables, so if it is feasible to make a figure, make a figure. To avoid confusing the reader, either avoid abbreviations in tables and figures, or define them in a footnote. Note that there should not be citations in the results section and you should not interpret results here. Table 3 provides common results section pitfalls and recommendations for addressing them.

Discussion Section

Opposite the introduction section, the discussion should take the form of a right-side-up triangle beginning with interpretation of your results and moving to general implications (Fig.  2 ). This section typically begins with a restatement of the main findings, which can usually be accomplished with a few carefully-crafted sentences.

Major elements of the discussion section of an original research article. Often, the elements overlap

Next, interpret the meaning or explain the significance of your results, lifting the reader’s gaze from the study’s specific findings to more general applications. Then, compare these study findings with other research. Are these findings in agreement or disagreement with those from other studies? Does this study impart additional nuance to well-accepted theories? Situate your findings within the broader context of scientific literature, then explain the pathways or mechanisms that might give rise to, or explain, the results.

Journals vary in their approach to strengths and limitations sections: some are embedded paragraphs within the discussion section, while some mandate separate section headings. Keep in mind that every study has strengths and limitations. Candidly reporting yours helps readers to correctly interpret your research findings.

The next element of the discussion is a summary of the potential impacts and applications of the research. Should these results be used to optimally design an intervention? Does the work have implications for clinical protocols or public policy? These considerations will help the reader to further grasp the possible impacts of the presented work.

Finally, the discussion should conclude with specific suggestions for future work. Here, you have an opportunity to illuminate specific gaps in the literature that compel further study. Avoid the phrase “future research is necessary” because the recommendation is too general to be helpful to readers. Instead, provide substantive and specific recommendations for future studies. Table 4 provides common discussion section pitfalls and recommendations for addressing them.

Follow the Journal’s Author Guidelines

After you select a target journal, identify the journal’s author guidelines to guide the formatting of your manuscript and references. Author guidelines will often (but not always) include instructions for titles, cover letters, and other components of a manuscript submission. Read the guidelines carefully. If you do not follow the guidelines, your article will be sent back to you.

Finally, do not submit your paper to more than one journal at a time. Even if this is not explicitly stated in the author guidelines of your target journal, it is considered inappropriate and unprofessional.

Your title should invite readers to continue reading beyond the first page [ 4 , 5 ]. It should be informative and interesting. Consider describing the independent and dependent variables, the population and setting, the study design, the timing, and even the main result in your title. Because the focus of the paper can change as you write and revise, we recommend you wait until you have finished writing your paper before composing the title.

Be sure that the title is useful for potential readers searching for your topic. The keywords you select should complement those in your title to maximize the likelihood that a researcher will find your paper through a database search. Avoid using abbreviations in your title unless they are very well known, such as SNP, because it is more likely that someone will use a complete word rather than an abbreviation as a search term to help readers find your paper.

After you have written a complete draft, use the checklist (Fig. 3 ) below to guide your revisions and editing. Additional resources are available on writing the abstract and citing references [ 5 ]. When you feel that your work is ready, ask a trusted colleague or two to read the work and provide informal feedback. The box below provides a checklist that summarizes the key points offered in this article.

Checklist for manuscript quality

Data Availability

Michalek AM (2014) Down the rabbit hole…advice to reviewers. J Cancer Educ 29:4–5

Article   Google Scholar  

International Committee of Medical Journal Editors. Defining the role of authors and contributors: who is an author? http://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-authosrs-and-contributors.html . Accessed 15 January, 2020

Vetto JT (2014) Short and sweet: a short course on concise medical writing. J Cancer Educ 29(1):194–195

Brett M, Kording K (2017) Ten simple rules for structuring papers. PLoS ComputBiol. https://doi.org/10.1371/journal.pcbi.1005619

Lang TA (2017) Writing a better research article. J Public Health Emerg. https://doi.org/10.21037/jphe.2017.11.06

Download references

Acknowledgments

Ella August is grateful to the Sustainable Sciences Institute for mentoring her in training researchers on writing and publishing their research.

Code Availability

Not applicable.

Author information

Authors and affiliations.

Department of Maternal and Child Health, University of North Carolina Gillings School of Global Public Health, 135 Dauer Dr, 27599, Chapel Hill, NC, USA

Clara Busse & Ella August

Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, 48109-2029, USA

Ella August

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to Ella August .

Ethics declarations

Conflicts of interests.

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

(PDF 362 kb)

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Busse, C., August, E. How to Write and Publish a Research Paper for a Peer-Reviewed Journal. J Canc Educ 36 , 909–913 (2021). https://doi.org/10.1007/s13187-020-01751-z

Download citation

Published : 30 April 2020

Issue Date : October 2021

DOI : https://doi.org/10.1007/s13187-020-01751-z

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Manuscripts
• Scientific writing
• Find a journal
• Publish with us
• Track your research

Have a language expert improve your writing

Run a free plagiarism check in 10 minutes, generate accurate citations for free.

• Knowledge Base
• Research paper

Writing a Research Paper Introduction | Step-by-Step Guide

Published on September 24, 2022 by Jack Caulfield . Revised on March 27, 2023.

The introduction to a research paper is where you set up your topic and approach for the reader. It has several key goals:

• Present your topic and get the reader interested
• Provide background or summarize existing research
• Position your own approach
• Detail your specific research problem and problem statement
• Give an overview of the paper’s structure

The introduction looks slightly different depending on whether your paper presents the results of original empirical research or constructs an argument by engaging with a variety of sources.

Instantly correct all language mistakes in your text

Upload your document to correct all your mistakes in minutes

Table of contents

Step 1: introduce your topic, step 2: describe the background, step 3: establish your research problem, step 4: specify your objective(s), step 5: map out your paper, research paper introduction examples, frequently asked questions about the research paper introduction.

The first job of the introduction is to tell the reader what your topic is and why it’s interesting or important. This is generally accomplished with a strong opening hook.

The hook is a striking opening sentence that clearly conveys the relevance of your topic. Think of an interesting fact or statistic, a strong statement, a question, or a brief anecdote that will get the reader wondering about your topic.

For example, the following could be an effective hook for an argumentative paper about the environmental impact of cattle farming:

A more empirical paper investigating the relationship of Instagram use with body image issues in adolescent girls might use the following hook:

Don’t feel that your hook necessarily has to be deeply impressive or creative. Clarity and relevance are still more important than catchiness. The key thing is to guide the reader into your topic and situate your ideas.

Don't submit your assignments before you do this

The academic proofreading tool has been trained on 1000s of academic texts. Making it the most accurate and reliable proofreading tool for students. Free citation check included.

Try for free

This part of the introduction differs depending on what approach your paper is taking.

In a more argumentative paper, you’ll explore some general background here. In a more empirical paper, this is the place to review previous research and establish how yours fits in.

Argumentative paper: Background information

After you’ve caught your reader’s attention, specify a bit more, providing context and narrowing down your topic.

Provide only the most relevant background information. The introduction isn’t the place to get too in-depth; if more background is essential to your paper, it can appear in the body .

Empirical paper: Describing previous research

For a paper describing original research, you’ll instead provide an overview of the most relevant research that has already been conducted. This is a sort of miniature literature review —a sketch of the current state of research into your topic, boiled down to a few sentences.

This should be informed by genuine engagement with the literature. Your search can be less extensive than in a full literature review, but a clear sense of the relevant research is crucial to inform your own work.

Begin by establishing the kinds of research that have been done, and end with limitations or gaps in the research that you intend to respond to.

The next step is to clarify how your own research fits in and what problem it addresses.

Argumentative paper: Emphasize importance

In an argumentative research paper, you can simply state the problem you intend to discuss, and what is original or important about your argument.

Empirical paper: Relate to the literature

In an empirical research paper, try to lead into the problem on the basis of your discussion of the literature. Think in terms of these questions:

• What research gap is your work intended to fill?
• What limitations in previous work does it address?
• What contribution to knowledge does it make?

You can make the connection between your problem and the existing research using phrases like the following.

Now you’ll get into the specifics of what you intend to find out or express in your research paper.

The way you frame your research objectives varies. An argumentative paper presents a thesis statement, while an empirical paper generally poses a research question (sometimes with a hypothesis as to the answer).

Argumentative paper: Thesis statement

The thesis statement expresses the position that the rest of the paper will present evidence and arguments for. It can be presented in one or two sentences, and should state your position clearly and directly, without providing specific arguments for it at this point.

Empirical paper: Research question and hypothesis

The research question is the question you want to answer in an empirical research paper.

Present your research question clearly and directly, with a minimum of discussion at this point. The rest of the paper will be taken up with discussing and investigating this question; here you just need to express it.

A research question can be framed either directly or indirectly.

• This study set out to answer the following question: What effects does daily use of Instagram have on the prevalence of body image issues among adolescent girls?
• We investigated the effects of daily Instagram use on the prevalence of body image issues among adolescent girls.

If your research involved testing hypotheses , these should be stated along with your research question. They are usually presented in the past tense, since the hypothesis will already have been tested by the time you are writing up your paper.

For example, the following hypothesis might respond to the research question above:

Scribbr Citation Checker New

The AI-powered Citation Checker helps you avoid common mistakes such as:

• Missing commas and periods
• Incorrect usage of “et al.”
• Ampersands (&) in narrative citations
• Missing reference entries

The final part of the introduction is often dedicated to a brief overview of the rest of the paper.

In a paper structured using the standard scientific “introduction, methods, results, discussion” format, this isn’t always necessary. But if your paper is structured in a less predictable way, it’s important to describe the shape of it for the reader.

If included, the overview should be concise, direct, and written in the present tense.

• This paper will first discuss several examples of survey-based research into adolescent social media use, then will go on to …
• This paper first discusses several examples of survey-based research into adolescent social media use, then goes on to …

Full examples of research paper introductions are shown in the tabs below: one for an argumentative paper, the other for an empirical paper.

• Argumentative paper
• Empirical paper

Are cows responsible for climate change? A recent study (RIVM, 2019) shows that cattle farmers account for two thirds of agricultural nitrogen emissions in the Netherlands. These emissions result from nitrogen in manure, which can degrade into ammonia and enter the atmosphere. The study’s calculations show that agriculture is the main source of nitrogen pollution, accounting for 46% of the country’s total emissions. By comparison, road traffic and households are responsible for 6.1% each, the industrial sector for 1%. While efforts are being made to mitigate these emissions, policymakers are reluctant to reckon with the scale of the problem. The approach presented here is a radical one, but commensurate with the issue. This paper argues that the Dutch government must stimulate and subsidize livestock farmers, especially cattle farmers, to transition to sustainable vegetable farming. It first establishes the inadequacy of current mitigation measures, then discusses the various advantages of the results proposed, and finally addresses potential objections to the plan on economic grounds.

The rise of social media has been accompanied by a sharp increase in the prevalence of body image issues among women and girls. This correlation has received significant academic attention: Various empirical studies have been conducted into Facebook usage among adolescent girls (Tiggermann & Slater, 2013; Meier & Gray, 2014). These studies have consistently found that the visual and interactive aspects of the platform have the greatest influence on body image issues. Despite this, highly visual social media (HVSM) such as Instagram have yet to be robustly researched. This paper sets out to address this research gap. We investigated the effects of daily Instagram use on the prevalence of body image issues among adolescent girls. It was hypothesized that daily Instagram use would be associated with an increase in body image concerns and a decrease in self-esteem ratings.

The introduction of a research paper includes several key elements:

• A hook to catch the reader’s interest
• Relevant background on the topic
• Details of your research problem

and your problem statement

• A thesis statement or research question
• Sometimes an overview of the paper

Don’t feel that you have to write the introduction first. The introduction is often one of the last parts of the research paper you’ll write, along with the conclusion.

This is because it can be easier to introduce your paper once you’ve already written the body ; you may not have the clearest idea of your arguments until you’ve written them, and things can change during the writing process .

The way you present your research problem in your introduction varies depending on the nature of your research paper . A research paper that presents a sustained argument will usually encapsulate this argument in a thesis statement .

A research paper designed to present the results of empirical research tends to present a research question that it seeks to answer. It may also include a hypothesis —a prediction that will be confirmed or disproved by your research.

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the “Cite this Scribbr article” button to automatically add the citation to our free Citation Generator.

Caulfield, J. (2023, March 27). Writing a Research Paper Introduction | Step-by-Step Guide. Scribbr. Retrieved August 19, 2024, from https://www.scribbr.com/research-paper/research-paper-introduction/

Is this article helpful?

Jack Caulfield

Other students also liked, writing strong research questions | criteria & examples, writing a research paper conclusion | step-by-step guide, research paper format | apa, mla, & chicago templates, "i thought ai proofreading was useless but..".

I've been using Scribbr for years now and I know it's a service that won't disappoint. It does a good job spotting mistakes”

Purdue Online Writing Lab Purdue OWL® College of Liberal Arts

Writing a Literature Review

Welcome to the Purdue OWL

This page is brought to you by the OWL at Purdue University. When printing this page, you must include the entire legal notice.

Copyright ©1995-2018 by The Writing Lab & The OWL at Purdue and Purdue University. All rights reserved. This material may not be published, reproduced, broadcast, rewritten, or redistributed without permission. Use of this site constitutes acceptance of our terms and conditions of fair use.

A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

• An introductory paragraph that explains what your working topic and thesis is
• A forecast of key topics or texts that will appear in the review
• Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
• Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
• Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
• Critically Evaluate: Mention the strengths and weaknesses of your sources
• Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

• Summarize the key findings you have taken from the literature and emphasize their significance
• Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

• Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
• Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
• Qualitative versus quantitative research
• Empirical versus theoretical scholarship
• Divide the research by sociological, historical, or cultural sources
• Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

• It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
• Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
• Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
• Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

How To Skim Read Journal Articles

Fast-Track Your Literature Review By Focusing On Three Sections

By: Derek Jansen (MBA) | May 2020

If you’ve just started your literature review process, you’re probably sitting on a pile of scientific journal articles and research papers that are (1) lengthy and (2) written in very dense , academic language that is difficult to digest (at the best of times). It’s intimidating, for sure – and you’re probably wondering how on earth you’re going to get through it all.

You might be asking yourself some of these questions:

• Do I need to read every journal article to make sure I cover everything?
• Do I need to read every section of each article to understand it?
• If not, which sections should I focus on?

First things first, relax (I can feel your tension!). In this post, I’m going answer these questions and explain how to approach your review of the literature the smart way , so that you focus only on the most relevant literature and don’t waste time on low-value activities.

So, grab a nice hot cup of coffee (or tea, or whatever – just no beers) and let’s take a look at those questions, one at a time.

Question 1:

Do i need to read every journal article on my topic when doing my literature review.

The good news is that you don’t need to read every single journal article on your topic. Doing so would just be a waste of your time, as you’re generally looking to understand the current state of the literature – not the full history of it.

But… and this is an important but. You do need to read quite a bit to make sure that you have a comprehensive view of the current state of the literature (and of knowledge) in your area of research.

Quality trumps quantity when it comes to reviewing the literature. In other words, you need to focus on reading the journal articles that are most cited (i.e. that other academics have referenced) in relation to your topic keyword(s). You should focus on articles that are recent, relevant and well cited .

But how do I know if an article is well cited?

Thankfully, you can check the number of citations for any article really easily using Google Scholar . Just enter the article title in Google Scholar and it will show you how many citations it has – here’s an example:

In fact, Google Scholar is a great way to find the key journal articles for any keyword (topic) in general, so chances are you’ll be using this to find your journal articles in the first place. Therefore, be sure to keep an eye on citation count while you’re sourcing articles. It would also be smart to dedicate a column to it in your literature review catalogue (you can download one for free here ) so that you can quickly filter and sort by citation count.

A quick caveat – citation count is not a perfect metric for the quality of a journal article (unfortunately there is no unicorn metric that indicates quality). While its usually a good indicator of how popular an article is, it doesn’t mean the findings of the article are perfect (remember, the Kardashians are popular too – enough said). To the contrary, it could indicate that there’s a lot of controversy regarding the findings (sounds like the Kardashians again).

So, long story short – don’t be conned by citation count alone. Be sure to also pay attention the to quality of the journal each article is published in (you can check journal rank here ), and pay attention to what other articles say about any given popular article.

Need a helping hand?

Question 2:

Do i need to read the full journal journal article when doing my literature review.

Some more good news – no, you don’t need to read every single word in each journal article you review as part of your literature review. When you’re just starting your literature review, you need to get a big picture view of what each journal article is saying (in other words, the key questions and findings). Generally you can get a good feel for this by reading a few key sections in each article (we’ll get to these next).

That said (ah, there had to be a catch, right?), as you refine your literature review and establish more of a focus, you’ll need to dive deeper into the most important articles. Some articles will be central to your research – but you probably still don’t need to read them from first page to the last.

Question 3:

Which sections of each journal article should i read.

To get a big-picture view of what any article is all about, there are three sections that are very useful. These three sections generally explain both what the article is about (i.e. what questions they were trying to answer) and what the findings were (i.e. what their answers were). This is exactly what you’re looking for, so these three sections provide a great way for you to save time during your literature review.

So, let’s take a look at the three sections:

1 – The abstract (or executive summary)

The abstract (which is located right up front) provides a high-level overview of what the article is about. This is giving you the first little taste of the soup , so to speak. Generally, it will discuss what the research objectives were was and why they were important. This will give you a clear indication of how relevant the article is to your specific research, so pay close attention.

Sometimes the abstract will also discuss the findings of the article (much like a thesis abstract ), but this is not always the case (yeah, the abstract can be such a tease sometimes). If it does, it’s a bonus. But even so, you should still read the other sections, as the abstract only provides a very high-level view, and can miss out on specific nuances of the research.

2 – The introduction section

The introduction section will go into more detail about the topic being investigated and why this is important for the field of research. This will help you understand a bit more detail about what exactly they were investigating and in what context . Context is really important, so pay close attention to that.

For example, they might be investigating your exact topic, but in a country other than your own, or a different industry. In that case, you’d know that you need to pay very close attention to exactly how they undertook their research.

So, make sure you pay close attention to the introduction chapter to fully understand the focus of the research and the context in which it took place . Both will be important when it comes to writing your literature review, as you’ll need to use this information to build your arguments.

3 – The conclusion

While the introduction section tells you what the high-level questions the researchers asked, the conclusion section tells you what answers they found . This provides you with something of a shortcut to grasping the gist of the article, without reading all the dull and dry detail – yeah, it’s a little cheeky, I know. Of course, the conclusion is not going to highlight every nuance of the analysis findings, so if the article is highly relevant to your research, you should make sure to also pay close attention to the analysis findings section.

In addition to the findings of the research, the conclusion section will generally also highlight areas that require further research . In other words, they’ll outline areas that genuinely require further academic investigation (aka research gaps ). This is a gold mine for refining your topic into something highly original and well-rooted in the existing literature – just make sure that the article is recent, or someone else may have already exploited the research gap. If you’re still looking to identify a research topic, be sure to check out our video covering that here .

By reviewing these three sections of each article, you’ll save yourself a lot of time, while still getting a good understanding of what each article is saying. Keep in mind that as your literature review progresses, you focus will narrow and you’ll develop a set of core highly relevant articles, which you should sink your teeth into more deeply.

Let’s Recap

In this post, we looked at how to read academic journal articles quickly and efficiently, to save you many hours of pain while undertaking your literature review.

The key takeaways to remember are:

• You don’t need to read every single journal article covering your topic – focus on the most popular, authoritative and recent ones
• You don’t need to read every word of every article. To start, you just need to get a high-level understanding of the literature, which you can get by focusing on three key areas in each journal article.
• The three sections of each journal article to review are the abstract , the introduction and the conclusion .
• Once you’ve narrowed down your focus and have a core set of highly relevant, highly authoritative articles, you can dive deeper into them, paying closer attention to the methodology and analysis findings.

And there you have it – now go on and hammer through that pile of articles at warp speed. While you’re at it, why not also check out our other posts and videos covering research topic ideation , dissertation and thesis proposal , literature review , methodology , analysis and more.

Psst… there’s more!

This post is an extract from our bestselling short course, Literature Review Bootcamp . If you want to work smart, you don't want to miss this .

28 Comments

Thanks Derek for the tips

Reviewing the Literature can be overwhelming if you do not have the plan or the right structure to navigate the pool of information

You’re most welcome, Aletta. All the best with your literature review.

I personally have found these tips as a key to my long standing problem of reading articles. Thanks a million times

Simple and easy to read guidance… funny too

Great to hear that, Rishen 🙂

Much appreciated Derek. I already realized I could not read everything, but you confirming that has brought a lot of relief.

Great to hear that, Mazwakhe 🙂

Derek sir, I’m really happy for you.You made me to think very smart and effective way to do the review of literature.

Thank you so much.

Dear Derek, thank you for your easy and straight forward guidance,

Thanks for the interesting and informative article

You’re most welcome, Sanoon. Glad it was useful.

Thanks for the insights, I am about to start my literature review and this article as well as the other material from GradCoach will help me on the jorney.

You’re most welcome! Good luck writing your literature review

It was a great and effective information.

Thank you that was very helpful. I am taking a directed studies summer course, and I have to submit a literature review by end of August. That article was short, straight to the point and interesting 🙂 thank you Derek

You’re welcome, Emy 🙂 Good luck with your studies!

Thanks Derek. Reading this article has given me a boost because I have been so stock on how to go about my literature review.Though I know I am not meant to read the whole article.But your explanation has given me a greater insight.

Thank you very much sir for your great explanation 😄 Hopefully I’ve enough diligence and courage to start

You’re most welcome, Felicia. Good luck with your research.

thanks, it was helpful.

Thanks Derek for doing such a wonderful job of helping. Blessings Bro!

Concise and applicable, nice! what a great help. I am now doing a literature review section on my thesis, I used to waste so much time on reading articles that is not relevant back and forth.

Thank for your great help!

Hi Derek, i am busy with my research literature. I submited my 1st draft but it was way irrelevant as per comments made by my supervisor… i gave myself time to find out where i diverted until i lesson to some of your videos. As we speak now, i am starting following the guidelines and i feel confident that i am on the right track now. Thanks a lot my brother

You’re most welcome 🙂

I can’t explain my mood when I realised I had to study more than 40 articles about my study field. It was indeed a game-changer. Thank you very much, Derek. Also, Kardashian was the best example that can be used for this situation :)))

Thank you for posting this. It truly takes a load off! I’m new to Doctoral research and peer review study and “Overwhelmed” doesn’t quite sum up how I felt. This is a tremendous help!

Thank you for the advice. Question, how do one keep count of all the articles considered from starting point to narrowed down. Manually, or is there another way?

Trackbacks/Pingbacks

• What Is A Literature Review (In A Dissertation Or Thesis) - Grad Coach - […] first step of any literature review is to hunt down and read through the existing research that’s relevant to your research…

Submit a Comment Cancel reply

Your email address will not be published. Required fields are marked *

Save my name, email, and website in this browser for the next time I comment.

• Print Friendly

How Many References Should a Research Paper Have? Study of 96,685 Articles

I analyzed a random sample of 96,685 full-text research papers, uploaded to PubMed Central between the years 2016 and 2021, in order to answer the question:

How many references should you cite when writing a research article?

I used the BioC API to download the data (see the References section below).

Here’s a summary of the key findings

1- The average number of references for a research paper is 45 , with 90% of research papers having between 8 and 102 references. However, this number depends a lot on study design . For instance, a systematic review typically has 49 references while a case report has only 24.

2- As a rule of thumb, consider citing 1 reference for every 95 words (or 4 sentences) .

3- The more research you do will be reflected in the number of references you use in your paper, since high-quality articles usually have 5 more references than the median .

How many references does a typical article have?

The histogram below shows that most research papers have between 25 to 50 references, and only a few exceed 100:

Because the distribution has a right tail, the median number of references becomes a more reliable metric than the mean. Here are a few other numbers that summarize the data:

From this table we can conclude that:

The median research paper has 39 references, and 50% of papers have between 25 and 56 references. An article can have as few as 1 reference as a minimum, and 911 references as a maximum.

Next, let’s see if the number of references depends on the study design.

Should the study design influence the number of references you use?

The table below shows that:

1- Secondary study designs (systematic reviews and meta-analyses) have the highest number of references (median = 49), which is to be expected as these articles review a large body of information.

2- Experimental, quasi-experimental and analytical designs typically have between 35 and 39 references.

3- Descriptive designs (case reports and case series) have the lowest number of references (median ≈ 25), which also makes sense as these describe the clinical story of a single (or a few) patient(s) and generally have a very short literature review section.

How often should you cite in a research paper?

Some journals may specify the maximum number of citations allowed. For instance, Nature allows articles to have at most 30 references in the main text [ Source ]. So make sure to check the authorship guidelines of the journal where you want to submit.

That being said, often is the case where we ask ourselves: am I taking too much information from outside sources? or maybe too few? So I would argue that it would be useful to know, for a given article size, how many references to cite.

If we measure the length of all the articles in our dataset combined and divide it by the total number of references, we get the following numbers:

On average, 1 reference is cited for every 95 words, that is 1 reference for every 4 sentences. In terms of paragraphs, an article has approximately 1.5 references for each paragraph.

Here’s a table that shows the median number of references cited for each word count category:

Does using more references make your article better?

Hypothesis 1: It is well-known that citing more resources is usually associated with more in-depth research, therefore, we would expect high-quality articles to include a higher number of references.

Hypothesis 2: Some experts believe that a good writing habit is to keep the number of references to a minimum (see: Essentials of Writing Biomedical Research Papers by Mimi Zeiger), so according to this hypothesis, high-quality articles should have, on average, fewer references.

Let’s find out what researchers are doing in practice and which hypothesis our data support.

In order to answer the question, I collected the journal impact factor (JIF) for 71,579 articles and divided the dataset into 2 groups:

• research papers published in low impact journals (JIF ≤ 3): this subset consisted of 34,758 articles
• research papers published in high impact journals (JIF > 3): this subset consisted of 36,821 articles

After controlling for study design, the group with JIF ≤ 3 had a median number of references of 37, while the group with JIF > 3 had a median of 44.

Remember that the median article overall had 39 references (as we saw above), so based on these results, we can conclude that:

High-quality articles, in general, have about 5 more references than the median article. So a comprehensive literature review and a more in-depth discussion section can make the difference between a good and an excellent research article.

• Comeau DC, Wei CH, Islamaj Doğan R, and Lu Z. PMC text mining subset in BioC: about 3 million full text articles and growing,  Bioinformatics , btz070, 2019.

Further reading

• How Old Should References Be? Based on 3,823,919 Examples
• Statistical Software Popularity in 40,582 Research Papers
• Programming Languages Popularity in 12,086 Research Papers
• Length of a Conclusion Section: Analysis of 47,810 Examples
• How Long Should a Research Paper Be? Data from 61,519 Examples

Academics Write Papers Arguing Over How Many People Read (And Cite) Their Papers

Studies about reading studies go back more than two decades

Rose Eveleth

Contributor

There are a lot of scientific papers out there. One estimate  puts the count at 1.8 million articles published each year, in about 28,000 journals. Who actually reads those papers? According to one 2007 study , not many people: half of academic papers are read only by their authors and journal editors, the study's authors write. 

But not all academics accept that they have an audience of three. There's a heated dispute around academic readership and citation—enough that there have been studies about reading studies going back for more than two decades.

In the  2007 study , the authors introduce their topic by noting that  “as many as 50% of papers are never read by anyone other than their authors, referees and journal editors.” They also claim that 90 percent of papers published are never cited. Some academics are unsurprised by these numbers. “ I distinctly remember focusing not so much on the hyper-specific nature of these research topics, but how it must feel as an academic to spend so much time on a topic so far on the periphery of human interest,” writes Aaron Gordon at Pacific Standard . “Academia’s incentive structure is such that it’s better to publish something than nothing,” he explains, even if that something is only read by you and your reviewers. 

But not everybody agrees these numbers are fair. The claim that half of papers are never cited comes first from a paper from 1990. “ Statistics compiled by the Philadelphia-based Institute for Scientific Information (ISI) indicate that 55% of the papers published between 1981 and 1985 in journals indexed by the institute received no citations at all in the 5 years after they were published,” David P. Hamilton wrote in Science . 

In 2008, a team found that the problem is likely getting worse . “ As more journal issues came online, the articles referenced tended to be more recent, fewer journals and articles were cited, and more of those citations were to fewer journals and articles.” But some researchers took issue with that study, arguing that using different methods you could get quite different results. “Our own extensive investigations on this phenomenon… show that Evans’ suggestions that researchers tend to concentrate on more recent and more cited papers does not hold at the aggregate level in the biomedical sciences, the natural sciences and engineering, or the social sciences,” the authors write. This group of researchers found that plenty of old papers, for instance, were racking up readers over time.

It seems like this should be an easy question to answer: all you have to do is count the number of citations each paper has. But it’s harder than you might think. There are entire papers themselves dedicated to figuring out how to do this efficiently and accurately. The point of the 2007 paper wasn’t to assert that 50 percent of studies are unread. It was actually about citation analysis and the ways that the internet is letting academics see more accurately who is reading and citing their papers. “Since the turn of the century, dozens of databases such as Scopus and Google Scholar have appeared, which allow the citation patterns of academic papers to be studied with unprecedented speed and ease,” the paper's authors wrote.

Hopefully, someone will figure out how to answer this question definitively, so academics can start arguing about something else. 

Get the latest stories in your inbox every weekday.

Rose Eveleth | | READ MORE

Rose Eveleth was a writer for Smart News and a producer/designer/ science writer/ animator based in Brooklyn. Her work has appeared in the New York Times , Scientific American , Story Collider , TED-Ed and OnEarth .

Title Page Setup

A title page is required for all APA Style papers. There are both student and professional versions of the title page. Students should use the student version of the title page unless their instructor or institution has requested they use the professional version. APA provides a student title page guide (PDF, 199KB) to assist students in creating their title pages.

Student title page

The student title page includes the paper title, author names (the byline), author affiliation, course number and name for which the paper is being submitted, instructor name, assignment due date, and page number, as shown in this example.

Title page setup is covered in the seventh edition APA Style manuals in the Publication Manual Section 2.3 and the Concise Guide Section 1.6

Related handouts

• Student Title Page Guide (PDF, 263KB)
• Student Paper Setup Guide (PDF, 3MB)

Student papers do not include a running head unless requested by the instructor or institution.

Follow the guidelines described next to format each element of the student title page.

Professional title page

The professional title page includes the paper title, author names (the byline), author affiliation(s), author note, running head, and page number, as shown in the following example.

Follow the guidelines described next to format each element of the professional title page.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• ScientificWorldJournal
• v.2024; 2024
• PMC10807936

Writing a Scientific Review Article: Comprehensive Insights for Beginners

Ayodeji amobonye.

1 Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, KwaZulu-Natal, Durban 4000, South Africa

2 Writing Centre, Durban University of Technology, P.O. Box 1334 KwaZulu-Natal, Durban 4000, South Africa

Japareng Lalung

3 School of Industrial Technology, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, Malaysia

Santhosh Pillai

Associated data.

The data and materials that support the findings of this study are available from the corresponding author upon reasonable request.

Review articles present comprehensive overview of relevant literature on specific themes and synthesise the studies related to these themes, with the aim of strengthening the foundation of knowledge and facilitating theory development. The significance of review articles in science is immeasurable as both students and researchers rely on these articles as the starting point for their research. Interestingly, many postgraduate students are expected to write review articles for journal publications as a way of demonstrating their ability to contribute to new knowledge in their respective fields. However, there is no comprehensive instructional framework to guide them on how to analyse and synthesise the literature in their niches into publishable review articles. The dearth of ample guidance or explicit training results in students having to learn all by themselves, usually by trial and error, which often leads to high rejection rates from publishing houses. Therefore, this article seeks to identify these challenges from a beginner's perspective and strives to plug the identified gaps and discrepancies. Thus, the purpose of this paper is to serve as a systematic guide for emerging scientists and to summarise the most important information on how to write and structure a publishable review article.

1. Introduction

Early scientists, spanning from the Ancient Egyptian civilization to the Scientific Revolution of the 16 th /17 th century, based their research on intuitions, personal observations, and personal insights. Thus, less time was spent on background reading as there was not much literature to refer to. This is well illustrated in the case of Sir Isaac Newton's apple tree and the theory of gravity, as well as Gregor Mendel's pea plants and the theory of inheritance. However, with the astronomical expansion in scientific knowledge and the emergence of the information age in the last century, new ideas are now being built on previously published works, thus the periodic need to appraise the huge amount of already published literature [ 1 ]. According to Birkle et al. [ 2 ], the Web of Science—an authoritative database of research publications and citations—covered more than 80 million scholarly materials. Hence, a critical review of prior and relevant literature is indispensable for any research endeavour as it provides the necessary framework needed for synthesising new knowledge and for highlighting new insights and perspectives [ 3 ].

Review papers are generally considered secondary research publications that sum up already existing works on a particular research topic or question and relate them to the current status of the topic. This makes review articles distinctly different from scientific research papers. While the primary aim of the latter is to develop new arguments by reporting original research, the former is focused on summarising and synthesising previous ideas, studies, and arguments, without adding new experimental contributions. Review articles basically describe the content and quality of knowledge that are currently available, with a special focus on the significance of the previous works. To this end, a review article cannot simply reiterate a subject matter, but it must contribute to the field of knowledge by synthesising available materials and offering a scholarly critique of theory [ 4 ]. Typically, these articles critically analyse both quantitative and qualitative studies by scrutinising experimental results, the discussion of the experimental data, and in some instances, previous review articles to propose new working theories. Thus, a review article is more than a mere exhaustive compilation of all that has been published on a topic; it must be a balanced, informative, perspective, and unbiased compendium of previous studies which may also include contrasting findings, inconsistencies, and conventional and current views on the subject [ 5 ].

Hence, the essence of a review article is measured by what is achieved, what is discovered, and how information is communicated to the reader [ 6 ]. According to Steward [ 7 ], a good literature review should be analytical, critical, comprehensive, selective, relevant, synthetic, and fully referenced. On the other hand, a review article is considered to be inadequate if it is lacking in focus or outcome, overgeneralised, opinionated, unbalanced, and uncritical [ 7 ]. Most review papers fail to meet these standards and thus can be viewed as mere summaries of previous works in a particular field of study. In one of the few studies that assessed the quality of review articles, none of the 50 papers that were analysed met the predefined criteria for a good review [ 8 ]. However, beginners must also realise that there is no bad writing in the true sense; there is only writing in evolution and under refinement. Literally, every piece of writing can be improved upon, right from the first draft until the final published manuscript. Hence, a paper can only be referred to as bad and unfixable when the author is not open to corrections or when the writer gives up on it.

According to Peat et al. [ 9 ], “everything is easy when you know how,” a maxim which applies to scientific writing in general and review writing in particular. In this regard, the authors emphasized that the writer should be open to learning and should also follow established rules instead of following a blind trial-and-error approach. In contrast to the popular belief that review articles should only be written by experienced scientists and researchers, recent trends have shown that many early-career scientists, especially postgraduate students, are currently expected to write review articles during the course of their studies. However, these scholars have little or no access to formal training on how to analyse and synthesise the research literature in their respective fields [ 10 ]. Consequently, students seeking guidance on how to write or improve their literature reviews are less likely to find published works on the subject, particularly in the science fields. Although various publications have dealt with the challenges of searching for literature, or writing literature reviews for dissertation/thesis purposes, there is little or no information on how to write a comprehensive review article for publication. In addition to the paucity of published information to guide the potential author, the lack of understanding of what constitutes a review paper compounds their challenges. Thus, the purpose of this paper is to serve as a guide for writing review papers for journal publishing. This work draws on the experience of the authors to assist early-career scientists/researchers in the “hard skill” of authoring review articles. Even though there is no single path to writing scientifically, or to writing reviews in particular, this paper attempts to simplify the process by looking at this subject from a beginner's perspective. Hence, this paper highlights the differences between the types of review articles in the sciences while also explaining the needs and purpose of writing review articles. Furthermore, it presents details on how to search for the literature as well as how to structure the manuscript to produce logical and coherent outputs. It is hoped that this work will ease prospective scientific writers into the challenging but rewarding art of writing review articles.

2. Benefits of Review Articles to the Author

Analysing literature gives an overview of the “WHs”: WHat has been reported in a particular field or topic, WHo the key writers are, WHat are the prevailing theories and hypotheses, WHat questions are being asked (and answered), and WHat methods and methodologies are appropriate and useful [ 11 ]. For new or aspiring researchers in a particular field, it can be quite challenging to get a comprehensive overview of their respective fields, especially the historical trends and what has been studied previously. As such, the importance of review articles to knowledge appraisal and contribution cannot be overemphasised, which is reflected in the constant demand for such articles in the research community. However, it is also important for the author, especially the first-time author, to recognise the importance of his/her investing time and effort into writing a quality review article.

Generally, literature reviews are undertaken for many reasons, mainly for publication and for dissertation purposes. The major purpose of literature reviews is to provide direction and information for the improvement of scientific knowledge. They also form a significant component in the research process and in academic assessment [ 12 ]. There may be, however, a thin line between a dissertation literature review and a published review article, given that with some modifications, a literature review can be transformed into a legitimate and publishable scholarly document. According to Gülpınar and Güçlü [ 6 ], the basic motivation for writing a review article is to make a comprehensive synthesis of the most appropriate literature on a specific research inquiry or topic. Thus, conducting a literature review assists in demonstrating the author's knowledge about a particular field of study, which may include but not be limited to its history, theories, key variables, vocabulary, phenomena, and methodologies [ 10 ]. Furthermore, publishing reviews is beneficial as it permits the researchers to examine different questions and, as a result, enhances the depth and diversity of their scientific reasoning [ 1 ]. In addition, writing review articles allows researchers to share insights with the scientific community while identifying knowledge gaps to be addressed in future research. The review writing process can also be a useful tool in training early-career scientists in leadership, coordination, project management, and other important soft skills necessary for success in the research world [ 13 ]. Another important reason for authoring reviews is that such publications have been observed to be remarkably influential, extending the reach of an author in multiple folds of what can be achieved by primary research papers [ 1 ]. The trend in science is for authors to receive more citations from their review articles than from their original research articles. According to Miranda and Garcia-Carpintero [ 14 ], review articles are, on average, three times more frequently cited than original research articles; they also asserted that a 20% increase in review authorship could result in a 40–80% increase in citations of the author. As a result, writing reviews can significantly impact a researcher's citation output and serve as a valuable channel to reach a wider scientific audience. In addition, the references cited in a review article also provide the reader with an opportunity to dig deeper into the topic of interest. Thus, review articles can serve as a valuable repository for consultation, increasing the visibility of the authors and resulting in more citations.

3. Types of Review Articles

The first step in writing a good literature review is to decide on the particular type of review to be written; hence, it is important to distinguish and understand the various types of review articles. Although scientific review articles have been classified according to various schemes, however, they are broadly categorised into narrative reviews, systematic reviews, and meta-analyses [ 15 ]. It was observed that more authors—as well as publishers—were leaning towards systematic reviews and meta-analysis while downplaying narrative reviews; however, the three serve different aims and should all be considered equally important in science [ 1 ]. Bibliometric reviews and patent reviews, which are closely related to meta-analysis, have also gained significant attention recently. However, from another angle, a review could also be of two types. In the first class, authors could deal with a widely studied topic where there is already an accumulated body of knowledge that requires analysis and synthesis [ 3 ]. At the other end of the spectrum, the authors may have to address an emerging issue that would benefit from exposure to potential theoretical foundations; hence, their contribution would arise from the fresh theoretical foundations proposed in developing a conceptual model [ 3 ].

3.1. Narrative Reviews

Narrative reviewers are mainly focused on providing clarification and critical analysis on a particular topic or body of literature through interpretative synthesis, creativity, and expert judgement. According to Green et al. [ 16 ], a narrative review can be in the form of editorials, commentaries, and narrative overviews. However, editorials and commentaries are usually expert opinions; hence, a beginner is more likely to write a narrative overview, which is more general and is also referred to as an unsystematic narrative review. Similarly, the literature review section of most dissertations and empirical papers is typically narrative in nature. Typically, narrative reviews combine results from studies that may have different methodologies to address different questions or to formulate a broad theoretical formulation [ 1 ]. They are largely integrative as strong focus is placed on the assimilation and synthesis of various aspects in the review, which may involve comparing and contrasting research findings or deriving structured implications [ 17 ]. In addition, they are also qualitative studies because they do not follow strict selection processes; hence, choosing publications is relatively more subjective and unsystematic [ 18 ]. However, despite their popularity, there are concerns about their inherent subjectivity. In many instances, when the supporting data for narrative reviews are examined more closely, the evaluations provided by the author(s) become quite questionable [ 19 ]. Nevertheless, if the goal of the author is to formulate a new theory that connects diverse strands of research, a narrative method is most appropriate.

3.2. Systematic Reviews

In contrast to narrative reviews, which are generally descriptive, systematic reviews employ a systematic approach to summarise evidence on research questions. Hence, systematic reviews make use of precise and rigorous criteria to identify, evaluate, and subsequently synthesise all relevant literature on a particular topic [ 12 , 20 ]. As a result, systematic reviews are more likely to inspire research ideas by identifying knowledge gaps or inconsistencies, thus helping the researcher to clearly define the research hypotheses or questions [ 21 ]. Furthermore, systematic reviews may serve as independent research projects in their own right, as they follow a defined methodology to search and combine reliable results to synthesise a new database that can be used for a variety of purposes [ 22 ]. Typically, the peculiarities of the individual reviewer, different search engines, and information databases used all ensure that no two searches will yield the same systematic results even if the searches are conducted simultaneously and under identical criteria [ 11 ]. Hence, attempts are made at standardising the exercise via specific methods that would limit bias and chance effects, prevent duplications, and provide more accurate results upon which conclusions and decisions can be made.

The most established of these methods is the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines which objectively defined statements, guidelines, reporting checklists, and flowcharts for undertaking systematic reviews as well as meta-analysis [ 23 ]. Though mainly designed for research in medical sciences, the PRISMA approach has gained wide acceptance in other fields of science and is based on eight fundamental propositions. These include the explicit definition of the review question, an unambiguous outline of the study protocol, an objective and exhaustive systematic review of reputable literature, and an unambiguous identification of included literature based on defined selection criteria [ 24 ]. Other considerations include an unbiased appraisal of the quality of the selected studies (literature), organic synthesis of the evidence of the study, preparation of the manuscript based on the reporting guidelines, and periodic update of the review as new data emerge [ 24 ]. Other methods such as PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols), MOOSE (Meta-analysis Of Observational Studies in Epidemiology), and ROSES (Reporting Standards for Systematic Evidence Syntheses) have since been developed for systematic reviews (and meta-analysis), with most of them being derived from PRISMA.

Consequently, systematic reviews—unlike narrative reviews—must contain a methodology section which in addition to all that was highlighted above must fully describe the precise criteria used in formulating the research question and setting the inclusion or exclusion criteria used in selecting/accessing the literature. Similarly, the criteria for evaluating the quality of the literature included in the review as well as for analysing, synthesising, and disseminating the findings must be fully described in the methodology section.

3.3. Meta-Analysis

Meta-analyses are considered as more specialised forms of systematic reviews. Generally, they combine the results of many studies that use similar or closely related methods to address the same question or share a common quantitative evaluation method [ 25 ]. However, meta-analyses are also a step higher than other systematic reviews as they are focused on numerical data and involve the use of statistics in evaluating different studies and synthesising new knowledge. The major advantage of this type of review is the increased statistical power leading to more reliable results for inferring modest associations and a more comprehensive understanding of the true impact of a research study [ 26 ]. Unlike in traditional systematic reviews, research topics covered in meta-analyses must be mature enough to allow the inclusion of sufficient homogeneous empirical research in terms of subjects, interventions, and outcomes [ 27 , 28 ].

Being an advanced form of systematic review, meta-analyses must also have a distinct methodology section; hence, the standard procedures involved in the traditional systematic review (especially PRISMA) also apply in meta-analyses [ 23 ]. In addition to the common steps in formulating systematic reviews, meta-analyses are required to describe how nested and missing data are handled, the effect observed in each study, the confidence interval associated with each synthesised effect, and any potential for bias presented within the sample(s) [ 17 ]. According to Paul and Barari [ 28 ], a meta-analysis must also detail the final sample, the meta-analytic model, and the overall analysis, moderator analysis, and software employed. While the overall analysis involves the statistical characterization of the relationships between variables in the meta-analytic framework and their significance, the moderator analysis defines the different variables that may affect variations in the original studies [ 28 , 29 ]. It must also be noted that the accuracy and reliability of meta-analyses have both been significantly enhanced by the incorporation of statistical approaches such as Bayesian analysis [ 30 ], network analysis [ 31 ], and more recently, machine learning [ 32 ].

3.4. Bibliometric Review

A bibliometric review, commonly referred to as bibliometric analysis, is a systematic evaluation of published works within a specific field or discipline [ 33 ]. This bibliometric methodology involves the use of quantitative methods to analyse bibliometric data such as the characteristics and numbers of publications, units of citations, authorship, co-authorship, and journal impact factors [ 34 ]. Academics use bibliometric analysis with different objectives in mind, which includes uncovering emerging trends in article and journal performance, elaborating collaboration patterns and research constituents, evaluating the impact and influence of particular authors, publications, or research groups, and highlighting the intellectual framework of a certain field [ 35 ]. It is also used to inform policy and decision-making. Similarly to meta-analysis, bibliometric reviews rely upon quantitative techniques, thus avoiding the interpretation bias that could arise from the qualitative techniques of other types of reviews [ 36 ]. However, while bibliometric analysis synthesises the bibliometric and intellectual structure of a field by examining the social and structural linkages between various research parts, meta-analysis focuses on summarising empirical evidence by probing the direction and strength of effects and relationships among variables, especially in open research questions [ 37 , 38 ]. However, similarly to systematic review and meta-analysis, a bibliometric review also requires a well-detailed methodology section. The amount of data to be analysed in bibliometric analysis is quite massive, running to hundreds and tens of thousands in some cases. Although the data are objective in nature (e.g., number of citations and publications and occurrences of keywords and topics), the interpretation is usually carried out through both objective (e.g., performance analysis) and subjective (e.g., thematic analysis) evaluations [ 35 ]. However, the invention and availability of bibliometric software such as BibExcel, Gephi, Leximancer, and VOSviewer and scientific databases such as Dimensions, Web of Science, and Scopus have made this type of analysis more feasible.

3.5. Patent Review

Patent reviews provide a comprehensive analysis and critique of a specific patent or a group of related patents, thus presenting a concise understanding of the technology or innovation that is covered by the patent [ 39 ]. This type of article is useful for researchers as it also enhances their understanding of the legal, technical, and commercial aspects of an intellectual property/innovation; in addition, it is also important for stakeholders outside the research community including IP (intellectual property) specialists, legal professionals, and technology-transfer officers [ 40 ]. Typically, patent reviews encompass the scope, background, claims, legal implications, technical specifications, and potential commercial applications of the patent(s). The article may also include a discussion of the patent's strengths and weaknesses, as well as its potential impact on the industry or field in which it operates. Most times, reviews are time specified, they may be regionalised, and the data are usually retrieved via patent searches on databases such as that of the European Patent Office ( https://www.epo.org/searching.html ), United States Patent and Trademark Office ( https://patft.uspto.gov/ ), the World Intellectual Property Organization's PATENTSCOPE ( https://patentscope.wipo.int/search/en/structuredSearch.jsf ), Google Patent ( https://www.google.com/?tbm=pts ), and China National Intellectual Property Administration ( https://pss-system.cponline.cnipa.gov.cn/conventionalSearch ). According to Cerimi et al. [ 41 ], the retrieved data and analysed may include the patent number, patent status, filing date, application date, grant dates, inventor, assignee, and pending applications. While data analysis is usually carried out by general data software such as Microsoft Excel, an intelligence software solely dedicated to patent research and analysis, Orbit Intelligence has been found to be more efficient [ 39 ]. It is also mandatory to include a methodology section in a patent review, and this should be explicit, thorough, and precise to allow a clear understanding of how the analysis was carried out and how the conclusions were arrived at.

4. Searching Literature

One of the most challenging tasks in writing a review article on a subject is the search for relevant literature to populate the manuscript as the author is required to garner information from an endless number of sources. This is even more challenging as research outputs have been increasing astronomically, especially in the last decade, with thousands of new articles published annually in various fields. It is therefore imperative that the author must not only be aware of the overall trajectory in a field of investigation but must also be cognizant of recent studies so as not to publish outdated research or review articles. Basically, the search for the literature involves a coherent conceptual structuring of the topic itself and a thorough collation of evidence under the common themes which might reflect the histories, conflicts, standoffs, revolutions, and/or evolutions in the field [ 7 ]. To start the search process, the author must carefully identify and select broad keywords relevant to the subject; subsequently, the keywords should be developed to refine the search into specific subheadings that would facilitate the structure of the review.

Two main tactics have been identified for searching the literature, namely, systematic and snowballing [ 42 ]. The systematic approach involves searching literature with specific keywords (for example, cancer, antioxidant, and nanoparticles), which leads to an almost unmanageable and overwhelming list of possible sources [ 43 ]. The snowballing approach, however, involves the identification of a particular publication, followed by the compilation of a bibliography of articles based on the reference list of the identified publication [ 44 ]. Many times, it might be necessary to combine both approaches, but irrespective, the author must keep an accurate track and record of papers cited in the search. A simple and efficient strategy for populating the bibliography of review articles is to go through the abstract (and sometimes the conclusion) of a paper; if the abstract is related to the topic of discourse, the author might go ahead and read the entire article; otherwise, he/she is advised to move on [ 45 ]. Winchester and Salji [ 5 ] noted that to learn the background of the subject/topic to be reviewed, starting literature searches with academic textbooks or published review articles is imperative, especially for beginners. Furthermore, it would also assist in compiling the list of keywords, identifying areas of further exploration, and providing a glimpse of the current state of the research. However, past reviews ideally are not to serve as the foundation of a new review as they are written from someone else's viewpoint, which might have been tainted with some bias. Fortunately, the accessibility and search for the literature have been made relatively easier than they were a few decades ago as the current information age has placed an enormous volume of knowledge right at our fingertips [ 46 ]. Nevertheless, when gathering the literature from the Internet, authors should exercise utmost caution as much of the information may not be verified or peer-reviewed and thus may be unregulated and unreliable. For instance, Wikipedia, despite being a large repository of information with more than 6.7 million articles in the English language alone, is considered unreliable for scientific literature reviews, due to its openness to public editing [ 47 ]. However, in addition to peer-reviewed journal publications—which are most ideal—reviews can also be drawn from a wide range of other sources such as technical documents, in-house reports, conference abstracts, and conference proceedings. Similarly, “Google Scholar”—as against “Google” and other general search engines—is more appropriate as its searches are restricted to only academic articles produced by scholarly societies or/and publishers [ 48 ]. Furthermore, the various electronic databases, such as ScienceDirect, Web of Science, PubMed, and MEDLINE, many of which focus on specific fields of research, are also ideal options [ 49 ]. Advancement in computer indexing has remarkably expanded the ease and ability to search large databases for every potentially relevant article. In addition to searching by topic, literature search can be modified by time; however, there must be a balance between old papers and recent ones. The general consensus in science is that publications less than five years old are considered recent.

It is important, especially in systematic reviews and meta-analyses, that the specific method of running the computer searches be properly documented as there is the need to include this in the method (methodology) section of such papers. Typically, the method details the keywords, databases explored, search terms used, and the inclusion/exclusion criteria applied in the selection of data and any other specific decision/criteria. All of these will ensure the reproducibility and thoroughness of the search and the selection procedure. However, Randolph [ 10 ] noted that Internet searches might not give the exhaustive list of articles needed for a review article; hence, it is advised that authors search through the reference lists of articles that were obtained initially from the Internet search. After determining the relevant articles from the list, the author should read through the references of these articles and repeat the cycle until saturation is reached [ 10 ]. After populating the articles needed for the literature review, the next step is to analyse them individually and in their whole entirety. A systematic approach to this is to identify the key information within the papers, examine them in depth, and synthesise original perspectives by integrating the information and making inferences based on the findings. In this regard, it is imperative to link one source to the other in a logical manner, for instance, taking note of studies with similar methodologies, papers that agree, or results that are contradictory [ 42 ].

5. Structuring the Review Article

The title and abstract are the main selling points of a review article, as most readers will only peruse these two elements and usually go on to read the full paper if they are drawn in by either or both of the two. Tullu [ 50 ] recommends that the title of a scientific paper “should be descriptive, direct, accurate, appropriate, interesting, concise, precise, unique, and not be misleading.” In addition to providing “just enough details” to entice the reader, words in the titles are also used by electronic databases, journal websites, and search engines to index and retrieve a particular paper during a search [ 51 ]. Titles are of different types and must be chosen according to the topic under review. They are generally classified as descriptive, declarative, or interrogative and can also be grouped into compound, nominal, or full-sentence titles [ 50 ]. The subject of these categorisations has been extensively discussed in many articles; however, the reader must also be aware of the compound titles, which usually contain a main title and a subtitle. Typically, subtitles provide additional context—to the main title—and they may specify the geographic scope of the research, research methodology, or sample size [ 52 ].

Just like primary research articles, there are many debates about the optimum length of a review article's title. However, the general consensus is to keep the title as brief as possible while not being too general. A title length between 10 and 15 words is recommended, since longer titles can be more challenging to comprehend. Paiva et al. [ 53 ] observed that articles which contain 95 characters or less get more views and citations. However, emphasis must be placed on conciseness as the audience will be more satisfied if they can understand what exactly the review has contributed to the field, rather than just a hint about the general topic area. Authors should also endeavour to stick to the journal's specific requirements, especially regarding the length of the title and what they should or should not contain [ 9 ]. Thus, avoidance of filler words such as “a review on/of,” “an observation of,” or “a study of” is a very simple way to limit title length. In addition, abbreviations or acronyms should be avoided in the title, except the standard or commonly interpreted ones such as AIDS, DNA, HIV, and RNA. In summary, to write an effective title, the authors should consider the following points. What is the paper about? What was the methodology used? What were the highlights and major conclusions? Subsequently, the author should list all the keywords from these answers, construct a sentence from these keywords, and finally delete all redundant words from the sentence title. It is also possible to gain some ideas by scanning indices and article titles in major journals in the field. It is important to emphasise that a title is not chosen and set in stone, and the title is most likely to be continually revised and adjusted until the end of the writing process.

5.2. Abstract

The abstract, also referred to as the synopsis, is a summary of the full research paper; it is typically independent and can stand alone. For most readers, a publication does not exist beyond the abstract, partly because abstracts are often the only section of a paper that is made available to the readers at no cost, whereas the full paper may attract a payment or subscription [ 54 ]. Thus, the abstract is supposed to set the tone for the few readers who wish to read the rest of the paper. It has also been noted that the abstract gives the first impression of a research work to journal editors, conference scientific committees, or referees, who might outright reject the paper if the abstract is poorly written or inadequate [ 50 ]. Hence, it is imperative that the abstract succinctly represents the entire paper and projects it positively. Just like the title, abstracts have to be balanced, comprehensive, concise, functional, independent, precise, scholarly, and unbiased and not be misleading [ 55 ]. Basically, the abstract should be formulated using keywords from all the sections of the main manuscript. Thus, it is pertinent that the abstract conveys the focus, key message, rationale, and novelty of the paper without any compromise or exaggeration. Furthermore, the abstract must be consistent with the rest of the paper; as basic as this instruction might sound, it is not to be taken for granted. For example, a study by Vrijhoef and Steuten [ 56 ] revealed that 18–68% of 264 abstracts from some scientific journals contained information that was inconsistent with the main body of the publications.

Abstracts can either be structured or unstructured; in addition, they can further be classified as either descriptive or informative. Unstructured abstracts, which are used by many scientific journals, are free flowing with no predefined subheadings, while structured abstracts have specific subheadings/subsections under which the abstract needs to be composed. Structured abstracts have been noted to be more informative and are usually divided into subsections which include the study background/introduction, objectives, methodology design, results, and conclusions [ 57 ]. No matter the style chosen, the author must carefully conform to the instructions provided by the potential journal of submission, which may include but are not limited to the format, font size/style, word limit, and subheadings [ 58 ]. The word limit for abstracts in most scientific journals is typically between 150 and 300 words. It is also a general rule that abstracts do not contain any references whatsoever.

Typically, an abstract should be written in the active voice, and there is no such thing as a perfect abstract as it could always be improved on. It is advised that the author first makes an initial draft which would contain all the essential parts of the paper, which could then be polished subsequently. The draft should begin with a brief background which would lead to the research questions. It might also include a general overview of the methodology used (if applicable) and importantly, the major results/observations/highlights of the review paper. The abstract should end with one or few sentences about any implications, perspectives, or future research that may be developed from the review exercise. Finally, the authors should eliminate redundant words and edit the abstract to the correct word count permitted by the journal [ 59 ]. It is always beneficial to read previous abstracts published in the intended journal, related topics/subjects from other journals, and other reputable sources. Furthermore, the author should endeavour to get feedback on the abstract especially from peers and co-authors. As the abstract is the face of the whole paper, it is best that it is the last section to be finalised, as by this time, the author would have developed a clearer understanding of the findings and conclusions of the entire paper.

5.3. Graphical Abstracts

Since the mid-2000s, an increasing number of journals now require authors to provide a graphical abstract (GA) in addition to the traditional written abstract, to increase the accessibility of scientific publications to readers [ 60 ]. A study showed that publications with GA performed better than those without it, when the abstract views, total citations, and downloads were compared [ 61 ]. However, the GA should provide “a single, concise pictorial, and visual summary of the main findings of an article” [ 62 ]. Although they are meant to be a stand-alone summary of the whole paper, it has been noted that they are not so easily comprehensible without having read through the traditionally written abstract [ 63 ]. It is important to note that, like traditional abstracts, many reputable journals require GAs to adhere to certain specifications such as colour, dimension, quality, file size, and file format (usually JPEG/JPG, PDF, PNG, or TIFF). In addition, it is imperative to use engaging and accurate figures, all of which must be synthesised in order to accurately reflect the key message of the paper. Currently, there are various online or downloadable graphical tools that can be used for creating GAs, such as Microsoft Paint or PowerPoint, Mindthegraph, ChemDraw, CorelDraw, and BioRender.

5.4. Keywords

As a standard practice, journals require authors to select 4–8 keywords (or phrases), which are typically listed below the abstract. A good set of keywords will enable indexers and search engines to find relevant papers more easily and can be considered as a very concise abstract [ 64 ]. According to Dewan and Gupta [ 51 ], the selection of appropriate keywords will significantly enhance the retrieval, accession, and consequently, the citation of the review paper. Ideally, keywords can be variants of the terms/phrases used in the title, the abstract, and the main text, but they should ideally not be the exact words in the main title. Choosing the most appropriate keywords for a review article involves listing down the key terms and phrases in the article, including abbreviations. Subsequently, a quick review of the glossary/vocabulary/term list or indexing standard in the specific discipline will assist in selecting the best and most precise keywords that match those used in the databases from the list drawn. In addition, the keywords should not be broad or general terms (e.g., DNA, biology, and enzymes) but must be specific to the field or subfield of study as well as to the particular paper [ 65 ].

5.5. Introduction

The introduction of an article is the first major section of the manuscript, and it presents basic information to the reader without compelling them to study past publications. In addition, the introduction directs the reader to the main arguments and points developed in the main body of the article while clarifying the current state of knowledge in that particular area of research [ 12 ]. The introduction part of a review article is usually sectionalised into background information, a description of the main topic and finally a statement of the main purpose of the review [ 66 ]. Authors may begin the introduction with brief general statements—which provide background knowledge on the subject matter—that lead to more specific ones [ 67 ]. It is at this point that the reader's attention must be caught as the background knowledge must highlight the importance and justification for the subject being discussed, while also identifying the major problem to be addressed [ 68 ]. In addition, the background should be broad enough to attract even nonspecialists in the field to maximise the impact and widen the reach of the article. All of these should be done in the light of current literature; however, old references may also be used for historical purposes. A very important aspect of the introduction is clearly stating and establishing the research problem(s) and how a review of the particular topic contributes to those problem(s). Thus, the research gap which the paper intends to fill, the limitations of previous works and past reviews, if available, and the new knowledge to be contributed must all be highlighted. Inadequate information and the inability to clarify the problem will keep readers (who have the desire to obtain new information) from reading beyond the introduction [ 69 ]. It is also pertinent that the author establishes the purpose of reviewing the literature and defines the scope as well as the major synthesised point of view. Furthermore, a brief insight into the criteria used to select, evaluate, and analyse the literature, as well as the outline or sequence of the review, should be provided in the introduction. Subsequently, the specific objectives of the review article must be presented. The last part of the “introduction” section should focus on the solution, the way forward, the recommendations, and the further areas of research as deduced from the whole review process. According to DeMaria [ 70 ], clearly expressed or recommended solutions to an explicitly revealed problem are very important for the wholesomeness of the “introduction” section. It is believed that following these steps will give readers the opportunity to track the problems and the corresponding solution from their own perspective in the light of current literature. As against some suggestions that the introduction should be written only in present tenses, it is also believed that it could be done with other tenses in addition to the present tense. In this regard, general facts should be written in the present tense, specific research/work should be in the past tense, while the concluding statement should be in the past perfect or simple past. Furthermore, many of the abbreviations to be used in the rest of the manuscript and their explanations should be defined in this section.

5.6. Methodology

Writing a review article is equivalent to conducting a research study, with the information gathered by the author (reviewer) representing the data. Like all major studies, it involves conceptualisation, planning, implementation, and dissemination [ 71 ], all of which may be detailed in a methodology section, if necessary. Hence, the methodological section of a review paper (which can also be referred to as the review protocol) details how the relevant literature was selected and how it was analysed as well as summarised. The selection details may include, but are not limited to, the database consulted and the specific search terms used together with the inclusion/exclusion criteria. As earlier highlighted in Section 3 , a description of the methodology is required for all types of reviews except for narrative reviews. This is partly because unlike narrative reviews, all other review articles follow systematic approaches which must ensure significant reproducibility [ 72 ]. Therefore, where necessary, the methods of data extraction from the literature and data synthesis must also be highlighted as well. In some cases, it is important to show how data were combined by highlighting the statistical methods used, measures of effect, and tests performed, as well as demonstrating heterogeneity and publication bias [ 73 ].

The methodology should also detail the major databases consulted during the literature search, e.g., Dimensions, ScienceDirect, Web of Science, MEDLINE, and PubMed. For meta-analysis, it is imperative to highlight the software and/or package used, which could include Comprehensive Meta-Analysis, OpenMEE, Review Manager (RevMan), Stata, SAS, and R Studio. It is also necessary to state the mathematical methods used for the analysis; examples of these include the Bayesian analysis, the Mantel–Haenszel method, and the inverse variance method. The methodology should also state the number of authors that carried out the initial review stage of the study, as it has been recommended that at least two reviews should be done blindly and in parallel, especially when it comes to the acquisition and synthesis of data [ 74 ]. Finally, the quality and validity assessment of the publication used in the review must be stated and well clarified [ 73 ].

5.7. Main Body of the Review

Ideally, the main body of a publishable review should answer these questions: What is new (contribution)? Why so (logic)? So what (impact)? How well it is done (thoroughness)? The flow of the main body of a review article must be well organised to adequately maintain the attention of the readers as well as guide them through the section. It is recommended that the author should consider drawing a conceptual scheme of the main body first, using methods such as mind-mapping. This will help create a logical flow of thought and presentation, while also linking the various sections of the manuscript together. According to Moreira [ 75 ], “reports do not simply yield their findings, rather reviewers make them yield,” and thus, it is the author's responsibility to transform “resistant” texts into “docile” texts. Hence, after the search for the literature, the essential themes and key concepts of the review paper must be identified and synthesised together. This synthesis primarily involves creating hypotheses about the relationships between the concepts with the aim of increasing the understanding of the topic being reviewed. The important information from the various sources should not only be summarised, but the significance of studies must be related back to the initial question(s) posed by the review article. Furthermore, MacLure [ 76 ] stated that data are not just to be plainly “extracted intact” and “used exactly as extracted,” but must be modified, reconfigured, transformed, transposed, converted, tabulated, graphed, or manipulated to enable synthesis, combination, and comparison. Therefore, different pieces of information must be extracted from the reports in which they were previously deposited and then refined into the body of the new article [ 75 ]. To this end, adequate comparison and combination might require that “qualitative data be quantified” or/and “quantitative data may be qualitized” [ 77 ]. In order to accomplish all of these goals, the author may have to transform, paraphrase, generalize, specify, and reorder the text [ 78 ]. For comprehensiveness, the body paragraphs should be arranged in a similar order as it was initially stated in the abstract or/and introduction. Thus, the main body could be divided into thematic areas, each of which could be independently comprehensive and treated as a mini review. Similarly, the sections can also be arranged chronologically depending on the focus of the review. Furthermore, the abstractions should proceed from a wider general view of the literature being reviewed and then be narrowed down to the specifics. In the process, deep insights should also be provided between the topic of the review and the wider subject area, e.g., fungal enzymes and enzymes in general. The abstractions must also be discussed in more detail by presenting more specific information from the identified sources (with proper citations of course!). For example, it is important to identify and highlight contrary findings and rival interpretations as well as to point out areas of agreement or debate among different bodies of literature. Often, there are previous reviews on the same topic/concept; however, this does not prevent a new author from writing one on the same topic, especially if the previous reviews were written many years ago. However, it is important that the body of the new manuscript be written from a new angle that was not adequately covered in the past reviews and should also incorporate new studies that have accumulated since the last review(s). In addition, the new review might also highlight the approaches, limitations, and conclusions of the past studies. But the authors must not be excessively critical of the past reviews as this is regarded by many authors as a sign of poor professionalism [ 3 , 79 ]. Daft [ 79 ] emphasized that it is more important for a reviewer to state how their research builds on previous work instead of outright claiming that previous works are incompetent and inadequate. However, if a series of related papers on one topic have a common error or research flaw that needs rectification, the reviewer must point this out with the aim of moving the field forward [ 3 ]. Like every other scientific paper, the main body of a review article also needs to be consistent in style, for example, in the choice of passive vs. active voice and present vs. past tense. It is also important to note that tables and figures can serve as a powerful tool for highlighting key points in the body of the review, and they are now considered core elements of reviews. For more guidance and insights into what should make up the contents of a good review article, readers are also advised to get familiarised with the Boote and Beile [ 80 ] literature review scoring rubric as well as the review article checklist of Short [ 81 ].

5.8. Tables and Figures

An ideal review article should be logically structured and efficiently utilise illustrations, in the form of tables and figures, to convey the key findings and relationships in the study. According to Tay [ 13 ], illustrations often take a secondary role in review papers when compared to primary research papers which are focused on illustrations. However, illustrations are very important in review articles as they can serve as succinct means of communicating major findings and insights. Franzblau and Chung [ 82 ] pointed out that illustrations serve three major purposes in a scientific article: they simplify complex data and relationships for better understanding, they minimise reading time by summarising and bringing to focus on the key findings (or trends), and last, they help to reduce the overall word count. Hence, inserting and constructing illustrations in a review article is as meticulous as it is important. However, important decisions should be made on whether the charts, figures, or tables to be potentially inserted in the manuscript are indeed needed and how best to design them [ 83 ]. Illustrations should enhance the text while providing necessary information; thus, the information described in illustrations should not contradict that in the main text and should also not be a repetition of texts [ 84 ]. Furthermore, illustrations must be autonomous, meaning they ought to be intelligible without having to read the text portion of the manuscript; thus, the reader does not have to flip back and forth between the illustration and the main text in order to understand it [ 85 ]. It should be noted that tables or figures that directly reiterate the main text or contain extraneous information will only make a mess of the manuscript and discourage readers [ 86 ].

Kotz and Cals [ 87 ] recommend that the layout of tables and figures should be carefully designed in a clear manner with suitable layouts, which will allow them to be referred to logically and chronologically in the text. In addition, illustrations should only contain simple text, as lengthy details would contradict their initial objective, which was to provide simple examples or an overview. Furthermore, the use of abbreviations in illustrations, especially tables, should be avoided if possible. If not, the abbreviations should be defined explicitly in the footnotes or legends of the illustration [ 88 ]. Similarly, numerical values in tables and graphs should also be correctly approximated [ 84 ]. It is recommended that the number of tables and figures in the manuscript should not exceed the target journal's specification. According to Saver [ 89 ], they ideally should not account for more than one-third of the manuscript. Finally, the author(s) must seek permission and give credits for using an already published illustration when necessary. However, none of these are needed if the graphic is originally created by the author, but if it is a reproduced or an adapted illustration, the author must obtain permission from the copyright owner and include the necessary credit. One of the very important tools for designing illustrations is Creative Commons, a platform that provides a wide range of creative works which are available to the public for use and modification.

5.9. Conclusion/Future Perspectives

It has been observed that many reviews end abruptly with a short conclusion; however, a lot more can be included in this section in addition to what has been said in the major sections of the paper. Basically, the conclusion section of a review article should provide a summary of key findings from the main body of the manuscript. In this section, the author needs to revisit the critical points of the paper as well as highlight the accuracy, validity, and relevance of the inferences drawn in the article review. A good conclusion should highlight the relationship between the major points and the author's hypothesis as well as the relationship between the hypothesis and the broader discussion to demonstrate the significance of the review article in a larger context. In addition to giving a concise summary of the important findings that describe current knowledge, the conclusion must also offer a rationale for conducting future research [ 12 ]. Knowledge gaps should be identified, and themes should be logically developed in order to construct conceptual frameworks as well as present a way forward for future research in the field of study [ 11 ].

Furthermore, the author may have to justify the propositions made earlier in the manuscript, demonstrate how the paper extends past research works, and also suggest ways that the expounded theories can be empirically examined [ 3 ]. Unlike experimental studies which can only draw either a positive conclusion or ambiguous failure to reject the null hypothesis, four possible conclusions can be drawn from review articles [ 1 ]. First, the theory/hypothesis propounded may be correct after being proven from current evidence; second, the hypothesis may not be explicitly proven but is most probably the best guess. The third conclusion is that the currently available evidence does not permit a confident conclusion or a best guess, while the last conclusion is that the theory or hypothesis is false [ 1 ]. It is important not to present new information in the conclusion section which has link whatsoever with the rest of the manuscript. According to Harris et al. [ 90 ], the conclusions should, in essence, answer the question: if a reader were to remember one thing about the review, what would it be?

5.10. References

As it has been noted in different parts of this paper, authors must give the required credit to any work or source(s) of information that was included in the review article. This must include the in-text citations in the main body of the paper and the corresponding entries in the reference list. Ideally, this full bibliographical list is the last part of the review article, and it should contain all the books, book chapters, journal articles, reports, and other media, which were utilised in the manuscript. It has been noted that most journals and publishers have their own specific referencing styles which are all derived from the more popular styles such as the American Psychological Association (APA), Chicago, Harvard, Modern Language Association (MLA), and Vancouver styles. However, all these styles may be categorised into either the parenthetical or numerical referencing style. Although a few journals do not have strict referencing rules, it is the responsibility of the author to reference according to the style and instructions of the journal. Omissions and errors must be avoided at all costs, and this can be easily achieved by going over the references many times for due diligence [ 11 ]. According to Cronin et al. [ 12 ], a separate file for references can be created, and any work used in the manuscript can be added to this list immediately after being cited in the text [ 12 ]. In recent times, the emergence of various referencing management software applications such as Endnote, RefWorks, Mendeley, and Zotero has even made referencing easier. The majority of these software applications require little technical expertise, and many of them are free to use, while others may require a subscription. It is imperative, however, that even after using these software packages, the author must manually curate the references during the final draft, in order to avoid any errors, since these programs are not impervious to errors, particularly formatting errors.

6. Concluding Remarks

Writing a review article is a skill that needs to be learned; it is a rigorous but rewarding endeavour as it can provide a useful platform to project the emerging researcher or postgraduate student into the gratifying world of publishing. Thus, the reviewer must develop the ability to think critically, spot patterns in a large volume of information, and must be invested in writing without tiring. The prospective author must also be inspired and dedicated to the successful completion of the article while also ensuring that the review article is not just a mere list or summary of previous research. It is also important that the review process must be focused on the literature and not on the authors; thus, overt criticism of existing research and personal aspersions must be avoided at all costs. All ideas, sentences, words, and illustrations should be constructed in a way to avoid plagiarism; basically, this can be achieved by paraphrasing, summarising, and giving the necessary acknowledgments. Currently, there are many tools to track and detect plagiarism in manuscripts, ensuring that they fall within a reasonable similarity index (which is typically 15% or lower for most journals). Although the more popular of these tools, such as Turnitin and iThenticate, are subscription-based, there are many freely available web-based options as well. An ideal review article is supposed to motivate the research topic and describe its key concepts while delineating the boundaries of research. In this regard, experience-based information on how to methodologically develop acceptable and impactful review articles has been detailed in this paper. Furthermore, for a beginner, this guide has detailed “the why” and “the how” of authoring a good scientific review article. However, the information in this paper may as a whole or in parts be also applicable to other fields of research and to other writing endeavours such as writing literature review in theses, dissertations, and primary research articles. Finally, the intending authors must put all the basic rules of scientific writing and writing in general into cognizance. A comprehensive study of the articles cited within this paper and other related articles focused on scientific writing will further enhance the ability of the motivated beginner to deliver a good review article.

Acknowledgments

This work was supported by the National Research Foundation of South Africa under grant number UID 138097. The authors would like to thank the Durban University of Technology for funding the postdoctoral fellowship of the first author, Dr. Ayodeji Amobonye.

Data Availability

Conflicts of interest.

The authors declare that they have no conflicts of interest.

How to read scientific paper – a lot of them

A big learning curve for graduate students is reading the literature. I’ve seen student spend hours and days reading every single word of a scientific paper. And this is a good exercise for class, to learn all the parts and see all the things that you don’t know. But when you’re preparing your own research, this is no way to learn about an entire BODY of research and how your own project is related. Saying you have “read” a paper is not very meaningful, unless you can specifically cite a point in that paper that supports, corroborates, or conflicts with a hypothesis, method, or finding you wish to pursue.

So it is important to understand the difference between reading a single paper for the sake of learning about science, and what I call “reading with a purpose” for designing, conducting, and interpreting your own research. When you have specific questions that need to be answered, you don’t have to read every single word of a paper but it is better to understand the entirely of what has been done that is directly and indirectly related to your research. Remember that as you progress in your research you should expect to go back to some papers over an over again to check out different details relevant to your work, and you will develop a deeper understanding of it.

When I’m preparing for a grant especially in a new area, I like to do a search for relevant papers and sort them chronologically. Then a quick perusal of abstracts and citation metrics can help me understand the development of the field and key papers. One I can see the big picture, I hone in on critical papers establishing research questions and finding, and don’t spend much time on those that are subsequently filling in a single detail (most of them are like this). I keep notes on each paper, as relevant to the arguments that I would like to make, and the kinds of methodologies and findings that I can cite that paper for in my documents. You’ll learn to identify papers as Author, Date, Journal, which is the shorthand scientist use to communicate that they understand a particular line of research. Learn to associate key finding with those citations and also figure out what labs they come from (usually the last author). If you make a statement in a grant or paper, it MUST be substantiated through the citation of relevant literature. You’ll develop a set of a couple dozen papers that are most important for supporting your research based on the strength of prior research, as well as for establish the gaps that you will fill.

•  How to read a lot of papers

•  How to seriously read a scientific paper

•  How to critically review a paper

Fact-Checking Biden’s Speech and More: Day 1 of the Democratic National Convention

We followed the developments and fact-checked the speakers, providing context and explanation.

• Share full article

President Biden praised his administration’s accomplishments and declared his vice president a worthy successor on the first night of the Democratic National Convention on Monday.

Mr. Biden’s speech capped a night in which Democratic lawmakers and party stalwarts praised Vice President Kamala Harris, warned repeatedly that former President Donald J. Trump was unfit for office and celebrated Mr. Biden’s legacy.

Here’s a look at some of their claims.

“While schools closed and dead bodies filled morgues, Donald Trump downplayed the virus. He told us to inject bleach into our bodies. He peddled conspiracy theories across the country. We lost hundreds of thousands of Americans, and our economy collapsed.”

— Representative Robert Garcia of California

This is exaggerated.

Mr. Trump’s comments, in April 2020, about the efficacy of disinfectants and light as treatments for the coronavirus elicited uproar and confusion . He did not literally instruct people to inject bleach, but raised the suggestion as an “interesting” concept to test out.

At the April 2020 news conference , a member of Mr. Trump’s coronavirus task force said that the virus dies under direct sunlight and that applying bleach in indoor spaces kills the virus in five minutes and isopropyl alcohol does so in 30 seconds.

Mr. Trump responded: “Supposing we hit the body with a tremendous — whether it’s ultraviolet or just very powerful light — and I think you said that that hasn’t been checked, but you’re going to test it. And then I said, supposing you brought the light inside the body, which you can do either through the skin or in some other way, and I think you said you’re going to test that too.”

He added: “And then I see the disinfectant, where it knocks it out in a minute. One minute. And is there a way we can do something like that, by injection inside or almost a cleaning? Because you see it gets in the lungs and it does a tremendous number on the lungs. So it would be interesting to check that.”

Jeanna Smialek

“Trump talks big about bringing back manufacturing jobs, but you know who actually did it? President Biden and Vice President Kamala Harris.”

— Gov. Kathy Hochul of New York

This needs context .

It is true that manufacturing employment is up sharply under the Biden administration, but much of the gains are simply a recovery from job losses early in the coronavirus pandemic. Manufacturing employment is just slightly above its 2019 level. And factory employment also climbed somewhat from when Donald J. Trump took office in early 2017 and the onset of the pandemic in 2020.

Advertisement

“Thanks to Joe Biden and Kamala Harris, we reopened our schools.”

— Representative James E. Clyburn, Democrat of South Carolina

This needs context.

President Donald J. Trump and President Biden took different approaches to school reopenings during the coronavirus pandemic, with Mr. Trump encouraging schools to stay open and Mr. Biden emphasizing the need to contain the virus before reopening classroom doors. While they could signal policy preferences, developments in how the virus spread and how states and school districts reacted were sometimes out of their control.

The Centers for Disease Control and Prevention warned schools to prepare for disruption in February 2020, and a high school in Washington State became the first to close its doors that month . More schools across the country followed in adopting online instruction, but by the fall of 2020, some schools — often in states with Republican governors — returned to in-person instruction.

One audit found that by the fall of 2020 more schools had reverted to a traditional or hybrid model than remained virtual. A C.D.C. study found that school closures peaked in 2021, under the Biden administration, when the Omicron variant spread. By the fall of 2021, though, 98 percent of public schools were offering in-person instruction full time, according to the Education Department .

“Donald Trump wants to put our 1787 constitution through his Project 2025 paper shredder.”

— Representative Jasmine Crockett, Democrat of Texas

Project 2025, a set of conservative policy proposals assembled by a Washington think tank for a Republican presidential administration, does not directly come from Mr. Trump or his campaign.

Still, CNN documented instances where 140 people who worked for the Trump administration had a role in Project 2025. Some were top advisers to Mr. Trump in his first term and a re all but certain to step into prominent posts should he win a second term.

Mr. Trump has also supported some of the proposals, with even some overlap between Project 2025 and his own campaign plans. Among the similarities: undercutting the independence of the Justice Department and pressing to end diversity, equity and inclusion programs. And he enacted other initiatives mentioned in Project 2025 in his first term, such as levying tariffs on China and making it easier to fire federal workers.

But Mr. Trump has criticized some elements as “absolutely ridiculous and abysmal” though he has not specified which proposals he opposes. When the director of the project departed the think tank, Mr. Trump’s campaign released a statement that stated: “Reports of Project 2025’s demise would be greatly welcomed and should serve as notice to anyone or any group trying to misrepresent their influence with President Trump and his campaign — it will not end well for you.”

“JD Vance says women should stay in violent marriages and pregnancies resulting from rape are simply inconvenient.”

— Gov. Andy Beshear of Kentucky

Mr. Beshear was referring to comments Mr. Vance made during his 2022 campaign for Senate. Mr. Vance has rejected such interpretations.

In remarks to a Christian high school in California in September 2021, Mr. Vance spoke of his grandparents’ marriage, which he described in his memoir as violent.

“This is one of the great tricks that I think the sexual revolution pulled on the American populace, which is the idea that like, ‘Well, OK, these marriages were fundamentally, you know, they were maybe even violent, but certainly they were unhappy. And so getting rid of them and making it easier for people to shift spouses like they change their underwear, that’s going to make people happier in the long term,” he said .

Asked by Vice News about his remarks in 2022, Mr. Vance said, “Any fair person would recognize I was criticizing the progressive frame on this issue, not embracing it.”

He also told Fox News that Democrats had “twisted my words here” and that “it’s not what I believe, it’s not what I said.”

And regarding pregnancies resulting from rape, Mr. Vance told Fox News that he was criticizing the view that such pregnancies are “inconvenient.”

In a 2021 interview , Mr. Vance was asked whether abortion bans should have exceptions for rape or incest. He responded, “At the end of the day, we’re talking about an unborn baby. What kind of society do we want to have? A society that looks at unborn babies as inconveniences to be discarded?”

“Instead of paying $400 a month for insulin, seniors with diabetes will pay $35 a month.”

— President Biden

Mr. Biden signed a law that places a cap of $35 a month on insulin for all Medicare Part D beneficiaries. But he is overstating the average cost before the law.

Patients’ out-of-pocket spending on insulin was $434 on average for all of 2019 — not per month — and $449 per year for Medicare enrollees, according to the Health and Human Services Department .

“The smallest racial wealth gap in 20 years.”

As a percentage of wealth held by white families, Black and Latino families did grow to the largest amounts in 2022 in two decades. But the disparity in absolute dollar value actually increased.

“He called them ‘suckers and losers.’”

The claim that, as president, Donald J. Trump called veterans “suckers” and “losers” stems from a 2020 article in The Atlantic about his relationship to the military.

The article relied on anonymous sources, but many of the accounts have been corroborated by other outlets, including The New York Times, and by John F. Kelly, a retired four-star Marine general who served as Mr. Trump’s White House chief of staff. Mr. Trump has emphatically denied making the remarks since the article was published. Here’s a breakdown .

“Trump wants to cut Social Security and Medicare.”

This is misleading..

Mr. Trump has said repeatedly during his 2024 presidential campaign that he would not cut Social Security or Medicare, though he had previously shown brief and vague support for such proposals.

Asked about his position on the programs in relation to the national debt, Mr. Trump told CNBC in March, “There is a lot you can do in terms of entitlements in terms of cutting and in terms of also the theft and the bad management of entitlements.”

But Mr. Trump and his campaign clarified that he would not seek to cut the programs. Mr. Trump told the website Breitbart , “I will never do anything that will jeopardize or hurt Social Security or Medicare.” And during a July rally in Minnesota, he again vowed, “I will not cut one penny from Social Security or Medicare, and I will not raise the retirement age by one day, not by one day.”

Still, Mr. Trump has not outlined a clear plan for keeping the programs solvent. During his time in office, Mr. Trump did propose some cuts to Medicare — though experts said the cost reductions would not have significantly affected benefits — and to Social Security’s programs for people with disabilities. They were not enacted by Congress.

“He created the largest debt any president had in four years with his two trillion dollars tax cut for the wealthy.”

Looking at a single presidential term, Donald J. Trump’s administration did rack up more debt than any other in raw dollars — about $7.9 trillion . But the debt rose more under President Barack Obama’s eight years than under Mr. Trump’s four years. Also, when viewed as a percentage increase, the national debt rose more under President George H.W. Bush’s single term than under Mr. Trump’s.

The Congressional Budget Office estimated that Mr. Trump’s tax cuts — which passed in December 2017 with no Democrats in support — roughly added another $1 trillion to the federal deficit from 2018 to 2021, even after factoring in economic growth spurred by the tax cuts. But other drivers of the deficit include several sweeping measures that had bipartisan approval. The first coronavirus stimulus package , which received near unanimous support in Congress, added $2 trillion to the deficit over the next two fiscal years. Three additional spending measures contending with the coronavirus pandemic and its economic ramifications added another $1.4 trillion.

It is also important to note that presidents do not hold unilateral responsibility for the debt increase under their time in office. Policies from previous administrations — and programs such as Social Security and Medicare — continue to drive up debt, as do unexpected circumstances.

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Published: 19 June 2024

Why do patients with cancer die?

• Adrienne Boire   ORCID: orcid.org/0000-0002-9029-1248 1   na1 ,
• Katy Burke 2   na1 ,
• Thomas R. Cox   ORCID: orcid.org/0000-0001-9294-1745 3 , 4   na1 ,
• Theresa Guise 5   na1 ,
• Mariam Jamal-Hanjani 6 , 7 , 8   na1 ,
• Tobias Janowitz   ORCID: orcid.org/0000-0002-7820-3727 9 , 10   na1 ,
• Rosandra Kaplan 11   na1 ,
• Rebecca Lee   ORCID: orcid.org/0000-0003-2540-2009 12 , 13   na1 ,
• Charles Swanton   ORCID: orcid.org/0000-0002-4299-3018 7 , 8 , 14   na1 ,
• Matthew G. Vander Heiden   ORCID: orcid.org/0000-0002-6702-4192 15 , 16   na1 &
• Erik Sahai   ORCID: orcid.org/0000-0002-3932-5086 12   na1  

Nature Reviews Cancer volume  24 ,  pages 578–589 ( 2024 ) Cite this article

18k Accesses

1 Citations

525 Altmetric

Metrics details

• Cancer models
• Cancer therapy

Cancer is a major cause of global mortality, both in affluent countries and increasingly in developing nations. Many patients with cancer experience reduced life expectancy and have metastatic disease at the time of death. However, the more precise causes of mortality and patient deterioration before death remain poorly understood. This scarcity of information, particularly the lack of mechanistic insights, presents a challenge for the development of novel treatment strategies to improve the quality of, and potentially extend, life for patients with late-stage cancer. In addition, earlier deployment of existing strategies to prolong quality of life is highly desirable. In this Roadmap, we review the proximal causes of mortality in patients with cancer and discuss current knowledge about the interconnections between mechanisms that contribute to mortality, before finally proposing new and improved avenues for data collection, research and the development of treatment strategies that may improve quality of life for patients.

You have full access to this article via your institution.

Similar content being viewed by others

Causes of death among people living with metastatic cancer

Deceptive measures of progress in the NHS long-term plan for cancer: case-based vs. population-based measures

Changes in long term survival after diagnosis with common hematologic malignancies in the early 21st century

Introduction.

The phrase ‘metastasis accounts for 90% of cancer deaths’ is one of the most widely used in cancer research, yet it is overly simplistic, imprecise and it is difficult to find any primary analysis supporting the statement. Although patients with metastatic disease are overwhelmingly more likely to die than patients with non-metastatic cancer 1 , 2 , the determinants of cancer mortality are multifaceted and frequently involve dysfunction of multiple interconnected systems within the body. Understanding the mechanisms underpinning the causes of mortality, and subsequently intervening, has the potential to make cancer a less destructive disease, improving both the quality and length of life for patients with cancer. However, systematic analyses of the acute and root causes of mortality in patients with cancer are scarce, in part because death certificates rarely record enough information to understand the exact reason why the patient died beyond them having a malignancy. Causes of death may be simply listed as ‘metastatic carcinoma’ or ‘complications of cancer’, which give little insights into why a patient actually died. Potentially concomitant comorbidities are also not fully recorded. Even in cases in which the cause of death may be attributed to a single event, for example, a  thromboembolism , the underlying cause of that specific event may be complex. Indeed, metastatic cancer leads to perturbed function of multiple organ systems, and importantly, not just the organs to which disease has spread. This is probably due to the exuberant activation of local and systemic inflammatory, tissue repair and immune-suppressive programmes.

A simple view would be that death from metastatic disease correlates with the burden of disease. However, evidence suggests that the situation is more complex, with many factors influencing how metastases impact vital functions and ultimately lead to death. First, metastases to different organs will lead to different impacts on overall health. For example, brain metastases can lead to dysfunction of the central nervous system 3 , whereas peritoneal metastases may cause obstruction of the bowel 4 . In addition, the size or extent of metastases may not necessarily correlate with dysfunction of the organ where it is located 5 . Second, the production of the molecular mediators of organ dysfunction can vary between metastases and cancers of different origins. Third, individual patient characteristics such as age, sex, overall health, pre-existing comorbidities, genetics and socio-economic status vary 6 . Together, these factors directly influence the course of and physiological response to metastatic disease and can have profound indirect effects by limiting available treatment options and/or the ability of patients to tolerate or complete all intended treatment 7 , 8 . To understand why patients with cancer die, a closer examination of the factors contributing to mortality in patients with cancer and a dissection of the intricate web of causes that shape the frequency and dynamics of death are required.

Death may be related to an acute event, but the underlying mechanisms which trigger it may be modifiable or even preventable. In addition, other deaths may be the end stage of a continuum of deterioration, allowing the possibility of targeted intervention to improve quality of life. Moreover, it has been noted that early palliative care improves survival 9 . Ultimately, increased understanding of the processes occurring in patients with advanced disease should lead to improved strategies to minimize ill-health and suffering at the end of life. Coupled to this, patients and those around them should be enabled to have essential discussions about their wishes and preferences, minimizing potentially inappropriate treatments and maximizing quality of life 10 . Therefore, in this Roadmap, we briefly review data considering the immediate causes of mortality, highlight the intricate interconnections between different aspects of patient deterioration and conclude with recommendations for future studies of late-stage cancer that may shed new light on this important aspect of cancer biology and medicine.

Acute events leading to mortality

Although some cancers can be considered a chronic condition, with many patients living with their disease for years, the immediate cause of mortality can often be an acute event. Here, we briefly summarize common acute events leading to death in patients with cancer (Fig.  1 ). Although it is not possible to precisely determine, it is likely that the acute causes discussed subsequently may account for up to half of cancer deaths 11 , 12 . Immediate causes of mortality in other patients are less clear, with a more gradual deterioration typically occurring in vital organ systems (Fig.  1 ).

This schematic shows organs that frequently become dysfunctional in patients with late-stage cancer.

Vascular coagulation and cardiac failure

Patients with cancer are at an elevated risk of thromboembolism, which may trigger respiratory failure, fatal strokes, heart failure or myocardial infarction 13 . In some cases, disseminated intravascular coagulation can lead to thrombotic obstruction of small and midsize vessels leading to organ failure 14 . Haemorrhagic complications from depletion of platelets, via either immune or non-immune mechanisms 15 , 16 , and reduced levels of coagulation proteins can also be life-threatening 14 .  Congestive heart failure can also be a proximal cause of mortality, although the underlying causes are complex and include loss of cardiac muscle (associated with cachexia), shifts in intravascular fluid status and thromboembolic events 17 . Interestingly, bone metastases are particularly associated with cardiovascular problems, although the underlying mechanism remains unclear 18 . Comorbidities affecting the cardiovascular system may also make patients more prone to such events. Spatial occlusion of or invasion into vessels by cancer metastases can also lead to failure in blood supply or catastrophic haemorrhage 19 , 20 , 21 , 22 .

Displacement, functional impairment or obstruction of vital organs

The volume of disease may impair the function of a vital organ. This can be the case with brain metastases and glioblastoma or other primary brain cancers, with extensive invasion, brain herniation or oedema resulting in  midline shift or increased intracranial pressure irreversibly compromising brain function 22 , 23 , 24 . In addition, patients may develop seizures, which, if uncontrolled, can result in death 25 , 26 . However, this does not apply to all brain metastases, with  leptomeningeal metastases having minimal impact on intracranial pressure and brain structure; instead, these commonly obstruct cerebrospinal fluid flow and/or affect nerve function resulting in  hydrocephalus , deterioration of neurological function and death 26 .

Large lung metastases may impair the essential function of gas exchange. However, patients with miliary-like disease — characterized by nodules too numerous to count — can live with extensive disease in an organ with surprisingly little impact on function until a hard-to-predict tipping point is reached, which is then followed by rapid deterioration 27 . As with brain metastases, the volume of disease is often not sufficient to account for organ failure, as even a relatively small volume (<100 ml lung metastases volume compared with 4–5 l total lung volume) can be fatal 28 .  Lung oedema and pleural effusion are additional common contributors to death. Oedema may be caused by other pathologies such as infection or heart failure, whereas pleural effusion may be related to the presence of disease within the pleura as opposed to total tumour volume 28 , 29 .

Bowel obstruction can be a cause of mortality, especially in patients with peritoneal disease as found in particular in ovarian, colorectal and gastrointestinal cancers 30 . Both liver and kidney failure will also cause death in patients with cancer. Reasons for the failure of these organs include obstruction of the bile duct or ureters by metastases, therapy-induced toxicity leading to compromised normal organ function (discussed subsequently) and reduced tissue perfusion owing to hypotension or dehydration 31 , 32 , 33 , 34 . In addition, sepsis can result from obstruction of the bile ducts or ureters, which occurs unpredictably and often progresses rapidly leading to multiple organ failure and ultimately death.

Bacterial infections are the most common infection in patients with cancer, owing to impaired immune systems resulting from both the cancer itself and certain cancer treatments (discussed in detail subsequently), which induce myelosuppression and leukopenia. Patients with cancer can have an elevated risk of opportunistic viral, fungal and protozoal infections, which would typically be considered mild in healthy individuals, but which can cause serious life-threatening complications in those with cancer. Pneumonia and other lung infections leading to respiratory failure are often listed as causes of mortality in patients with cancer 35 , 36 . One of the most striking recent examples of this is the increased mortality observed in patients with cancer, particularly those with haematological cancers, who succumbed to COVID-19 compared with the general population 36 , 37 .

Paraneoplastic syndromes

Paraneoplastic syndromes are a group of rare disorders that can occasionally cause irreversible damage to critical organs and death. They are most associated with lung, breast, ovarian and lymphatic cancers, causing tissue or organ dysfunction at sites distinct from the location of the tumour 38 . Various mechanisms underpin paraneoplastic syndromes, including the inappropriate production of cytokines, hormones and antibodies. For example, excess parathyroid hormone-related protein (PTHRP) production by tumours can lead to hypercalcaemia 39 , 40 . Inappropriate anti-diuretic hormone production is commonly associated with small-cell lung cancer resulting in  hyponatraemia 41 . Furthermore, some neuroendocrine pancreatic tumours (insulinomas) secrete large amounts of insulin 42 . Tumours can also trigger the aberrant production of autoantibodies leading to disorders such as  Lambert–Eaton myasthenic syndrome (LEMS) or anti- N -methyl- d -aspartate receptor (NMDAR) encephalitis and myasthenia gravis 43 . Although treatment can usually manage the symptoms, in a subset of cases the syndromes cannot be controlled and are fatal 38 .

Therapy-induced toxicity

Although therapies are developed and administered with the intent of primarily targeting the tumour, almost all have some detrimental impact on normal tissue function. In some cases, the unintended consequences of therapy can be life-threatening. Autoimmune reactions resulting from targeting immune checkpoints can have fatal consequences, including  myocarditis and encephalitis 44 , 45 , 46 . Chemotherapy can lead to death as a result of acute neutropenic sepsis 47 . Depletion of platelets because of therapy can lead to fatal bleeding 16 . Arrhythmias, cardiomyopathy and coronary vasospasm are also a cause of death related to some anticancer treatments such as 5-fluorouracil and capecitabine 48 , 49 , 50 . The long-term detrimental effects of some therapies are discussed in detail subsequently.

Underlying causes

Determination of the proximal cause of mortality prompts further questions around the underlying factors giving rise to lethal pathology and ultimately how metastatic cancer triggers or accelerates those factors. In this section, we consider how chronic disruption of three major physiological organ systems is perturbed in patients with cancer and how these might contribute to mortality.

The immune and haematopoietic systems

In patients with cancer, the immune system becomes progressively less able to mount effective responses to infectious challenge, a phenomenon often generically termed ‘immune exhaustion’ (this usage is distinct from the more specific usage of immune exhaustion as a failure of tumour-reactive T cells to function). As a result, patients with metastatic disease have increased susceptibility to a wide range of infections and typically suffer more severe consequences than would otherwise be observed in healthy individuals 51 . Multiple mechanisms contribute to the reduced capability of the immune system to respond to infection. The presence of cancer cells in diverse organs triggers similar cellular and molecular events to wound responses 52 . The production of cytokines including interleukin 6 (IL-6), granulocyte colony-stimulating factor (GCSF) and granulocyte–macrophage colony-stimulating factor (GM–CSF), both by tumour cells and by other cells of the tumour microenvironment (TME), perturbs haematopoiesis leading to altered subsets of leukocytes 53 . Although, in the short term, this may have limited consequences on the ability of the body to respond to other challenges, prolonged disruption to haematopoiesis can strain the ability of haematopoietic stem cells (HSCs) to generate sufficient cells of the right type to cope with infections, with increased myeloid-to-lymphoid cell ratios.  Clonal haematopoiesis can be increased in patients with cancer, with myeloid skewing of immune cells and overall myeloid-mediated immune suppression and diminished naive T cell reservoirs 53 . Reduced production of platelets and altered iron metabolism leading to compromised oxygen carrying by red blood cells is also observed in many patients 54 . Other problems such as  immunoparesis can arise, with a high frequency observed in patients with multiple myeloma 55 .

T cell responses to infection are impaired in the presence of cancer with decreased proliferation and expression of granzyme B typically observed 56 . The chronic stimulation of T cells with neoantigens arising from ongoing mutational processes may also contribute to their weakened functionality. Moreover, immune surveillance of tumours inevitably selects for the production of immune suppressive factors by cancer cells, which further compound the issue 57 . Once again, comorbidities leading to either immune suppression or autoimmunity can intersect with the detrimental effects of cancer on the immune system.

Other consequences of cancer can indirectly result in an increased likelihood of infection. For example, vessel obstruction from cancer results in decreased flow of fluids such as bile, urine and lymph, creating environments in which bacteria can thrive 58 . Blockage of the bronchial tree can lead to pneumonia 59 . The invasive phenotype of cancer can result in  fistula formation (for example, rectovaginal in colorectal cancer), which enables bacteria to invade 60 . Furthermore, patients are often rendered bedbound or have limited mobility as cancer progresses, resulting in an increased chance of infections through decreased respiratory ventilation and atelectasis , as well as pressure sores and oedema 61 .

Disruption to haematopoiesis can also contribute to defects in coagulation and haemostasis . Elevated platelet numbers, termed thrombocytosis, are found in patients with cancer and are correlated with higher mortality 62 . The altered inflammatory cytokine milieu caused by the tumour may promote megakaryopoiesis, potentially through increasing thrombopoietin (TPO) production by the liver, and leading to higher platelet numbers. The risk of clotting can be further increased by the production of  tissue factor , which is responsible for initiating the clotting cascade, by tumour cells 63 . These mechanisms increase the likelihood of fatal thromboembolisms 63 .

Iatrogenic effects also have a role in the reduced immune function in patients with cancer. Cytotoxic therapies interfere with the proliferation and division of haematopoietic stem cells and can leave the immune system unable to mount effective responses to pathogens, leading to mortality 64 . In severe cases, pancytopenia results, marked by a substantial decrease in all three major blood cell lineages (red cells, white cells and platelets) 65 . This can lead to severe anaemia, increased infection susceptibility and increased likelihood of bleeding 47 , 66 , 67 . In other cases, more limited subsets of haematopoietic cells are affected. Thrombocytopenia — low platelet levels — leads to hypocoagulation and elevates the likelihood of haemorrhage 66 . Therefore, during cancer development and treatment, haemostasis mechanisms may be either augmented or attenuated; in both cases, the result is less predictable and less well-controlled coagulation. Neutropenia — low neutrophil levels — renders patients less able to fight infection and contributes to cancer mortality from infections that in many cases are thought to arise from resident mucosal flora 68 . Treatments, including chemotherapy and radiotherapy, often result in the breakdown of mucosal barriers (for example, oral mucositis) resulting in higher numbers of infections from pathogens, which normally reside on these surfaces 69 . In addition, corticosteroids, which are often given to alleviate symptoms or manage toxicity, can also contribute to the suppression of immune responses and compound the risk of infections in patients 70 . Clonal haematopoiesis, which as mentioned earlier is already more frequent in patients with cancer, can be further increased by chemotherapy 71 . More generally, cancer therapies can increase ageing-associated processes and reduce organ function 72 . Opioid pain relief administered to those with late-stage disease can also suppress the function of various bodily systems 73 . Finally, infections can arise owing to the insertion of drains and stents, or central venous catheters (CVCs; also known as lines) for the delivery of therapies. Infections from such lines are estimated to be around 0.5–10 per 1,000 CVC-days 74 , 75 .

Immunotherapies present a different set of immune complications from conventional therapies. These primarily relate to over-activation of the immune system leading to autoimmunity and, in some cases, cytokine storms that are treated with anti-cytokine therapies such as tocilizumab, anakinra and ruxilitinib, all of which can further suppress the immune response 76 . However, deaths attributable to autoimmune side effects of immune checkpoint inhibitors are rare (<1% in an analysis of more than 8,000 patients) especially if toxicity is managed promptly 77 , 78 . Colitis is a frequent problem, with disruption to colonic barrier function leading to increased susceptibility to perforation, which can be life-threatening.  Guillain–Barré syndrome , hepatitis and myocarditis are also causes of immune checkpoint inhibitor-related deaths 79 , 80 , 81 . Once again, high-dose corticosteroids are the main first-line treatment to manage autoimmune side effects in patients receiving immunotherapy and can lead to suppression of the immune system.  Hyperprogressive disease is observed in some patients following immunotherapy, the reasons for which are still being delineated, but there is probably a role for innate lymphoid cells releasing pro-growth cytokines 82 . Cell-based immunotherapies can also lead to disrupted bone marrow function and subsequent myelosuppression 83 .

The nervous system

The brain serves as a central nexus, orchestrating all vital functions. It is the hub of thought processes, emotions and sensory perception and regulates, directly or indirectly, everything from heartbeat and breathing to appetite. In addition to physical disruption of brain structure and intracranial pressure (discussed earlier) 84 , brain metastases impact the nervous system in multiple ways. Tumours in the brain or its surrounding tissues can substantially impair neural connections, leading to cognitive deficits, motor and sensory dysfunction, and even personality changes 84 , 85 , 86 . Interactions between brain metastases and neurons lead to changes in cortical function 87 , 88 , 89 . Even in regions of the brain without overt metastases, neuro-excitability can be increased, leading to changes in cognition, alertness and mood 90 . Tumours can slow the posterior dominant rhythm, leading to reduced alertness, loss of working memory and deterioration of quality of life 91 . Circadian rhythms are also impacted, leading to problems in memory and sleep, which is vital for the repair processes of the body that are essential for overall health and functioning 92 . Ultimately, many of these changes are not sustainable long-term. How these changes may lead to death is unclear, but they may follow similar trajectories to those in patients with dementia.

Brain function can also be disrupted in patients without brain metastases, with autonomic nervous system dysfunction often reported 93 . Intriguingly, anhedonia — a lack of ability to experience pleasure — occurs in many patients 94 . The mechanistic causes of this are unclear, but it is not restricted to patients with brain metastasis suggesting that circulating systemic factors may play a role. The wider effects of metastatic cancer on the mental well-being of a patient are discussed in Box  1 . However, beyond an effect on well-being, the disruption of brain function can contribute to anorexia, and reduced nutrition can influence many other physiological and pathophysiological processes 95 , 96 .

The role of the  peripheral nervous system in cancer-related death is not well described. Although the burgeoning field of cancer neuroscience provides evidence that the efferent system can support local and metastatic tumour growth 97 , 98 , 99 , at this time, it is unclear whether the reverse is also true. As mentioned earlier, there is clear evidence of autonomic nervous system dysfunction in patients with cancer 93 , raising the possibility that cancer-mediated interruption of afferent impulses might impact overall survival. Further studies are needed to explore this possibility.

Box 1 Psychosocial and societal factors contributing to the deterioration of patients with late-stage cancer

Psychological and social factors can have major and wide-ranging impacts on patients with incurable cancer. This manifests in more than threefold higher suicide rates 145 , 146 , 147 . Of note, these rates were further exacerbated in less advantaged sociodemographic groups 148 , arguing that financial issues and possibly health-care access are linked to suicide in patients with cancer. However, psychological symptoms are far more extensive than those captured in studies of suicide. Anhedonia and depression are frequent in patients with cancer, impacting their overall well-being, treatment adherence and outcomes including mortality 149 . These psychological challenges often intertwine with physical symptoms, compounding the burden of each 150 . Several studies have linked stress-related psychosocial factors to cancer mortality 151 , with recent work beginning to uncover the cellular and molecular mechanisms at play 152 .

Research on the psychosocial aspects of cancer care, including emotional and cognitive well-being, remains under-emphasized. Barriers to the integration of psychosocial care into cancer care include stigma, difficulty identifying substantial distress, limited access to evidence-based psychosocial treatments and concerns about cost 153 . Yet, an integrated system of psychosocial care including population-based screening and targeted treatment and access to good-quality palliative care improves emotional wellbeing 154 and physical symptoms 155 and is likely to be cost-saving 156 . A deeper understanding of the mechanisms underlying neuropsychological systems and insights into how metastatic disease impacts the physiological and chemical axes of the brain will be crucial. Such insights could inform tailored interventions, therapies and support structures that address the emotional toll of cancer, enhancing the holistic care approach and improving quality of life. Expanding psychosocial research can help bridge gaps in addressing mental health in patients with cancer, ultimately improving quality of life of patients during and after treatment 146 , 147 .

Metabolism and cachexia — catabolic effects of cancer

The presence of metastases presents altered energetic and anabolic demands on the body, leading to detrimental imbalances in metabolism 100 . Progressive and involuntary loss of body weight — termed cachexia — is a widespread multiorgan phenomenon commonly seen in patients with metastatic cancer 100 , 101 . This complex syndrome is characterized by a net negative energy balance, driven by the combination of increased energy expenditure and catabolism, with reduced appetite and caloric intake. A persistent decrease in nutrient intake is a key component across patients with many different cancer types, leading to breakdown of host tissues, with the degree of loss of adipose tissue and muscle mass varying between patients and among different cancer types 102 . However, the contribution of increased energy expenditure (as a result of tumour burden) is less clear.  Sarcopenia may be particularly prominent in some patients, possibly representing an independent pathology from other more global tissue wasting phenotypes, and in extreme cases, loss of cardiac or intercostal muscle mass can be fatal owing to insufficient cardiac or respiratory function, respectively 103 , 104 . These events have also been observed in the context of extreme starvation in patients with non-cancer conditions; for example, anorexia nervosa, in which cardiac dysfunction, in particular bradycardia and sinus pauses, can cause pulseless electrical activity and death 105 , 106 . Electrolyte disturbances and hypoglycaemia that are often observed in cases of severe malnutrition may exacerbate the risk of such arrhythmias 105 . Cachexia also has effects on other organs and tissues, including the brain and immune system 107 . Compromised immune function is a major consequence of starvation-induced tissue wasting 108 and suggests that altered systemic metabolism leading to, or associated with cachexia, may be a contributor to the immune dysfunction present in some patients with cancer 108 . Conversely, several studies have shown that both the brain and immune system can contribute to cachexia 100 , 101 .

Cachexia is multifactorial and has many potential causes. In some limited cases, tumour metabolism leads to systemic changes that increase energy usage. For example, high levels of lactate secretion by tumours can trigger the liver to convert lactate back to glucose, which requires energy input — termed the Cori cycle 109 . Such cycles can increase metabolic demand on the liver leading to further perturbation of liver function. However, cachexia does not correlate with disease volume in many cancer types 110 . Therefore, it is hard to reconcile a model in which the energetic and anabolic demands of the volume of disease are the main trigger for cachexia. Numerous studies have begun to reveal the possible molecular underpinnings of cachexia in some cancer types. Disruption of signalling by transforming growth factor-β (TGFβ) and related ligands is a recurring theme 111 , 112 , 113 . For example, circulating growth/differentiation factor 15 (GDF15; also known as MIC1), a highly conserved member of the TGFβ superfamily, is a known mediator of anorexia and weight loss, and increased circulating levels of this molecule in patients with lung cancer have been shown to correlate with cachexia development 114 . Clinical trials are currently underway to determine whether blockade of GDF15 ameliorates cachexia 115 . TGFβ itself can also promote muscle loss via the induction of myostatin 116 , and the induction of signalling by activin — another TGFβ superfamily ligand — can also have similar effects on muscle mass 117 , 118 . Furthermore, modulation of ryanodine receptor 1 (RYR1) downstream of TGFβ can perturb sarcomere organization and thereby lead to muscle weakness 111 . As such, preclinical studies have demonstrated the potential utility of TGFβ blockade in preventing cachexia 112 .

Elevated levels of cytokines, including tumour necrosis factor (TNF), IL-1 and IL-6, can also have roles in cachexia 119 , 120 , 121 . TNF induces multiple aspects of cachexia 122 . Muscle wasting is promoted through increased TNF and downstream nuclear factor-κB (NF-κB)-dependent ubiquitin-mediated proteolysis of muscle protein 123 , 124 . IL-6 triggers muscle loss through both NF-κB-dependent and JAK/STAT-dependent mechanisms 120 . Lipid metabolism is impacted by TNF reducing the expression of lipoprotein lipase and free fatty acid transporters, thereby reducing the accumulation of fat 125 . TNF can also reduce appetite through the production of  corticotropin-releasing hormone (CRH). IL-1, which triggers similar proximal changes in cell signalling to TNF, can activate many of the same processes 125 . It is also interesting to note that TGFβ, IL-1 and IL-6 are associated with programmes in cancer cells that drive metastasis, which could potentially explain why metastatic disease is linked to cachexia more strongly than the presence of primary disease alone.

Whole body dysfunction

Although consideration of different organ systems is useful for highlighting some of the key events contributing to cancer mortality, the interconnected nature of body systems and the pleiotropic characteristics of the molecular mediators at play mean that it is essential to consider whole body dysfunction when thinking about causes of cancer mortality. Furthermore, such analyses may explain cancer deaths without an acute proximal cause. As discussed earlier, cytokines with potent effects on the immune system, as well as effects on appetite, can be contributors to cachexia. Therefore, it is unsurprising that tumours impact both immune and metabolic function. The immune and nervous systems are highly sensitive to metabolite availability; for example, the brain has a high demand for glucose 108 , 126 . Several factors, including lactic acid production and kidney dysfunction, can lead to life-threatening systemic acidosis in patients with cancer, particularly haematological malignancies with high cell turnover 127 . These can be further exacerbated upon initiation of cytotoxic therapy resulting in  tumour lysis syndrome which can be fatal 128 . Consequently, metabolic perturbations and cachexia impact these systems. Over time, the cumulative stress of metabolic alterations caused by metastases, chronic changes in the level of cytokines, constant generation of tumour (neo)-antigens, aggressive therapies and incidental infections lead to exhaustion of the adaptive immune system and hamper the regenerative capacity of many organ systems with debilitating effects 18 . This multifaceted burden can ultimately trigger a body-wide shutdown leading to death.

Are mortality causes cancer-specific?

Although a subset of mortality causes are cancer-specific, such as metastatic invasion compromising specific organ function, the progressive and interconnected deterioration of multiple organ systems probably underlies many cancer-related deaths. This may be further influenced by interaction with other comorbidities. Of note, similar progressive deterioration is sometimes observed in the context of chronic infection and inflammation, with both cachexia and immune exhaustion associated with diseases such as tuberculosis (TB) and human immunodeficiency virus (HIV) infection 129 , 130 , 131 . This raises the question of whether the causes of death in patients with cancer are specific to cancer, or whether cancer (or any other chronic disease) is simply an accelerant of ageing processes occurring in healthy individuals. This hypothesis has practical implications because, if proven, it would suggest that lessons and approaches from other disease contexts could be readily transferable to patients with metastatic cancer. For example, the targeting or modulation of senescent cells is an active area of anti-ageing research, and numerous preclinical studies have indicated that similar strategies can attenuate the systemic effects of cancer 132 , 133 , 134 .

Recommendations

One goal of this Roadmap is to propose ways to improve our understanding of why patients with cancer die and thereby develop better strategies to ameliorate symptoms and prolong life with good quality. To this end, we propose that the following steps would be useful (Fig. 2 ).

This scheme shows how recommendations can interlink to provide both an improved understanding of the underlying biology behind late-stage cancer and strategies to improve quality of life of patients.

Improved records and reporting

It is notable that systematic reviews of the precise causes of cancer mortality are infrequent. This gap in knowledge, and recognition that this is often simply not known, is a major hindrance to learning and progress. Although improved accuracy of reporting on death certificates would be desirable, it would require a shift in longstanding clinical habits and may not be easily achievable in health-care systems under strain. Nonetheless, we advocate for locally enacting more consistency in death certificates, with specific acute causes included in addition to the underlying cause of cancer where known. Palliative care primarily focuses on symptom control for patients while balancing the potential benefits and burdens of additional diagnoses. Nevertheless, to address the gaps in our knowledge, it would be desirable to fund and establish prospective studies that continue active monitoring of patients as they transition from active disease treatment to palliative care. If possible, monitoring should be non-invasive as to not compromise patient comfort at the end of life. The great advances being made in patient monitoring with  wearable technologies might facilitate this and could be used for earlier detection of infections enabling quicker intervention. Caregiver involvement in reporting of symptoms may also play a role. Furthermore, consent to obtain more detailed information from the community and palliative care teams on the contributing factors to death would provide further insight. Patient and public engagement in this type of research will be critical, with studies indicating patient desire to participate in the right context 135 , 136 . In addition to information gathered before death, research autopsies have the potential to shed further light on the aetiology of death, such as thromboembolic events that may not have been detected in the absence of symptoms or diagnostic testing — discussed in Box  2 . Moreover, the availability of post-mortem samples can aid research into the biological underpinnings of metastases and processes leading to death. The greatest amount of information would be gained from cohorts additionally enrolled into warm autopsy programmes (Box  2 ).

Box 2 Research Autopsy Programmes and their optimization

Research autopsies are initiatives that involve the prompt collection of tissues from deceased individuals shortly after death, whereas tissue morphology is intact, and cells and tissues have not undergone substantial post-mortem changes. Research autopsy studies can be labour-intensive, and care is required in their logistical planning. The post-mortem interval (PMI) to autopsy can vary depending on the infrastructure available and can have implications for the utility of samples collected after death. For example, shorter PMIs achieved in rapid warm autopsy studies can more effectively facilitate in vitro (for example, cell line) and in vivo (for example, organoid and xenograft) models and can derive better quality RNA 157 , 158 . However, such studies are not easily established in the absence of out-of-hours facilities and expert input. Autopsies performed with longer PMIs, for example, up to several days after death, have been shown to have maintained tissue morphology and adequate DNA and RNA to facilitate cellular imaging techniques and genomic sequencing approaches 159 , 160 . Therefore, there is merit and general scientific value with autopsies regardless of the PMI, provided that consideration is given to the question being addressed, and the experimental approach.

The most powerful data are obtained from patients already involved in clinical studies before death. Information about disease course, longitudinal scans and tissue and blood analysis (cell counts, electrolytes, cytokines, metabolites and possibly circulating tumour DNA (ctDNA)) greatly enhances what can be learnt from post-mortem tissues. However, sensitivity is required to align the desire to acquire data with the wishes of the patients and their families, such that ultimately each autopsy has the potential to be meaningful and shed light on the biological processes leading to death.

More detailed observational clinical studies

Disease burden is not well correlated with survival; however, we propose that the accurate identification of prognostic factors correlating with survival should provide important insights into what ultimately precipitates mortality. As the cost of both targeted and non-targeted analyses of proteins and metabolites decreases, it should also become more feasible to explore molecular predictors of survival. Once identified, such factors could then be monitored in a targeted way prospectively with the potential to intervene where possible. In this setting, both the tumour and patient trajectory would receive precision-tailored treatments, the impact of which would need to be studied in randomized controlled trials. Even in the context of early phase trials, additional data could be obtained about patient symptoms in addition to safety considerations and tumour burden. Clinical imaging could also be exploited. Many patients receive computed tomography (CT) and positron-emission tomography (PET) scans, which contain abundant information about the burden and location of metastases and offer the opportunity to study changes in extent of adipose and muscle tissue and therefore body composition in relation to cachexia. Machine learning and artificial intelligence can be capitalized on to accurately measure these parameters, meaning that what would have previously been prohibitive owing to hours of radiologist time being required is now feasible 137 , 138 . In addition to the analysis of scans, the application of machine-learning approaches to metabolite, cytokine, immune cell and wearable technology-derived multimodal and multidimensional data may also uncover previously unknown parameters that correlate with mortality 139 . As outlined in Box  1 , incorporating psychosocial metrics into the study of late-stage cancer could also enable improvements in mental well-being of patients.

Increasing the relevance of model systems

Preclinical models will also have a place in determining the linkage between events found to precede death and cause of death; however, there should be an emphasis on reverse translation of questions from human studies to preclinical models. By way of example, this could involve modelling how metastases impinge on the ability of the body to respond to infection by challenging metastatic mouse models with a pathogen. Animal ethics and husbandry considerations mean that mice are housed in controlled environments in which exposure to pathogens is rare and the types of pathogen exposure are very narrow, so this type of information is currently lacking. To be optimally informative, practical and ethical complications around studying end-of-life physiology seen in patients need to be considered. Most models are chosen for their rapid progression, often with less than a month between primary or metastatic tumour seeding and death. These are not optimal for studying longer timescale chronic changes in patients. The development of slower progressing models, implementation of multiple lines of treatment and mimicking presence of other comorbidities should enable models to more accurately recapitulate observations made in patients. Furthermore, most preclinical cancer research currently uses young mice that fail to accurately mirror the interplay between ageing and cancer seen in humans 140 , with differences between chronological and immunological age providing a further confounding factor 141 . Researchers need to recognize the importance of and adopt more age-appropriate mouse models to better understand cancer mortality. In addition, most studies focus solely on tumour burden (which may only be possible at the point of death rather than longitudinally) or tumour size as a marker of disease, owing to the technical challenges of accurately quantifying organ impairment. Furthermore, tumour volume response and progression are poor surrogates of mortality in patients 142 ; therefore, better modelling of other metrics of tumour activity and impact on the body system may lead to better drug development. Minimizing and alleviating suffering in experimental animals is critical; hence ethical considerations limit the ability to study mortality in mice. Therefore, an expanded repertoire of analysis would help to understand how metastases impact specific systems and events, including the haematopoietic and nervous systems, as well as whole-body physiology and metabolism. Analysis of small volumes of blood can provide data on metabolites and cytokines, as well as complete blood counts (red blood cells, white blood cells and platelets), whereas increasingly sophisticated and automated technology is available to monitor mouse behaviour 143 . It is worth noting that weight loss is frequently used as a humane end point, which indicates that many cancer models trigger cachexia and that with appropriate measurements there is an opportunity to learn more about this phenomenon in existing models. We advocate more detailed reporting of why mice were culled in experimental studies — for example, tumour volume, weight loss, laboured breathing, complete blood cell counts and blood chemistry.

Clinical trials

The types of analyses detailed earlier will provide correlation between different factors and mortality, but not causative linkage. Ultimately, this information depends on testing in the context of clinical trials. Many of the mediators of immune dysfunction and cachexia can now be targeted with function blocking antibodies or forms of receptor traps and are being actively explored in clinical trials 115 , 144 . Several of these interventions were originally developed for chronic inflammatory conditions, which further highlights links between cancer and inflammation. The use of appropriately chosen secondary end points would provide an opportunity for testing whether correlative associations have a causal basis. In addition, many cancer drug trials stop providing an intervention at the point where a cancer progresses. The mechanisms behind cancer cachexia suggest that trials should be adapted to additionally consider clinical benefit in terms of weight, muscle loss and other specific determinants of efficacy, rather than solely monitor cancer progression.

Concluding remarks

Although efforts at cancer prevention and the development of curative treatment rightly receive considerable attention, we argue that understanding the precise events leading to cancer mortality should not be overlooked by funding bodies. Understanding the causes of dysfunction across multiple organ systems may provide novel strategies to manage symptoms of advanced cancer. Furthermore, better knowledge of the processes leading to death could enable patients and those around them to have essential discussions about their wishes and preferences, minimizing potentially inappropriate treatments and maximizing quality and enjoyment of life. In addition, more precise biomarkers of the likely timing of death may enable patients and their families to better utilize the time that is left. In the longer term, strategies to prevent organ dysfunction should offer considerable benefits to both patients with high tumour burden and those who have low disease burden but die from factors produced by cancer.

Dillekås, H., Rogers, M. S. & Straume, O. Are 90% of deaths from cancer caused by metastases? Cancer Med. 8 , 5574–5576 (2019).

Article   PubMed   PubMed Central   Google Scholar  

Seyfried, T. N. & Huysentruyt, L. C. On the origin of cancer metastasis. Crit. Rev. Oncog. 18 , 43–73 (2013).

Schnurman, Z. et al. Causes of death in patients with brain metastases. Neurosurgery 93 , 986–993 (2023).

Article   PubMed   Google Scholar  

Gallardo-Valverde, J. M. et al. Obstruction in patients with colorectal cancer increases morbidity and mortality in association with altered nutritional status. Nutr. Cancer 53 , 169–176 (2005).

Swanton, C. et al. Embracing cancer complexity: hallmarks of systemic disease. Cell 187 , 1589–1616 (2024).

Article   CAS   PubMed   Google Scholar  

Wheatley-Price, P., Blackhall, F. & Thatcher, N. The influence of sex in non-small cell lung cancer. Onkologie 32 , 547–548 (2009).

Abu-Sbeih, H. et al. Immune checkpoint inhibitor therapy in patients with preexisting inflammatory bowel disease. J. Clin. Oncol. 38 , 576 (2020).

Neugut, A. I. et al. Duration of adjuvant chemotherapy for colon cancer and survival among the elderly. J. Clin. Oncol. 24 , 2368–2375 (2006).

Sullivan, D. R. et al. Association of early palliative care use with survival and place of death among patients with advanced lung cancer receiving care in the Veterans Health Administration. JAMA Oncol. 5 , 1702–1709 (2019).

Sallnow, L. et al. Report of the Lancet Commission on the value of death: bringing death back into life. Lancet 399 , 837–884 (2022).

Abdel-Karim, I. A., Sammel, R. B. & Prange, M. A. Causes of death at autopsy in an inpatient hospice program. J. Palliat. Med. 10 , 894–898 (2007).

Pautex, S. et al. Anatomopathological causes of death in patients with advanced cancer: association with the use of anticoagulation and antibiotics at the end of life. J. Palliat. Med. 16 , 669–674 (2013).

Khorana, A. A., Francis, C. W., Culakova, E., Kuderer, N. M. & Lyman, G. H. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J. Thromb. Haemost. 5 , 632–634 (2007).

Levi, M. & Scully, M. How I treat disseminated intravascular coagulation. Blood 131 , 845–854 (2018).

Cines, D. B., Liebman, H. & Stasi, R. Pathobiology of secondary immune thrombocytopenia. Semin. Hematol. 46 , S2 (2009).

Ghanavat, M. et al. Thrombocytopenia in solid tumors: prognostic significance. Oncol. Rev. 13 , 43–48 (2019).

Article   CAS   Google Scholar  

Anker, M. S. et al. Advanced cancer is also a heart failure syndrome: a hypothesis. J. Cachexia Sarcopenia Muscle 12 , 533 (2021).

Asdahl, P. H. et al. Cardiovascular events in cancer patients with bone metastases — a Danish population-based cohort study of 23,113 patients. Cancer Med. 10 , 4885–4895 (2021).

Sinn, D. H. et al. Different survival of Barcelona clinic liver cancer stage C hepatocellular carcinoma patients by the extent of portal vein invasion and the type of extrahepatic spread. PLoS ONE 10 , e0124434 (2015).

Zisman, A. et al. Renal cell carcinoma with tumor thrombus extension: biology, role of nephrectomy and response to immunotherapy. J. Urol. 169 , 909–916 (2003).

Suárez, C. et al. Carotid blowout syndrome: modern trends in management. Cancer Manag. Res. 10 , 5617 (2018).

Lin, A. L. & Avila, E. K. Neurologic emergencies in the cancer patient: diagnosis and management. J. Intensive Care Med. 32 , 99 (2017).

Gamburg, E. S. et al. The prognostic significance of midline shift at presentation on survival in patients with glioblastoma multiforme. Int. J. Radiat. Oncol. Biol. Phys. 48 , 1359–1362 (2000).

Mokri, B. The Monro-Kellie hypothesis: applications in CSF volume depletion. Neurology 56 , 1746–1748 (2001).

Mastall, M. et al. Survival of brain tumour patients with epilepsy. Brain 144 , 3322–3327 (2021).

Steindl, A. et al. Neurological symptom burden impacts survival prognosis in patients with newly diagnosed non-small cell lung cancer brain metastases. Cancer 126 , 4341–4352 (2020).

Girard, N. et al. Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases. Am. J. Surg. Pathol. 33 , 1752–1764 (2009).

Lee, P. et al. Metabolic tumor burden predicts for disease progression and death in lung cancer. Int. J. Radiat. Oncol. Biol. Phys. 69 , 328–333 (2007).

Kookoolis, A. S., Puchalski, J. T., Murphy, T. E., Araujo, K. L. & Pisani, M. A. Mortality of hospitalized patients with pleural effusions. J. Pulm. Respir. Med. 4 , 184 (2014).

PubMed   PubMed Central   Google Scholar  

Cousins, S. E., Tempest, E. & Feuer, D. J. Surgery for the resolution of symptoms in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer. Cochrane Database Syst. Rev . https://doi.org/10.1002/14651858.CD002764 (2016).

Baker, M. L. et al. Mortality after acute kidney injury and acute interstitial nephritis in patients prescribed immune checkpoint inhibitor therapy. J. Immunother. Cancer 10 , e004421 (2022).

Bhave, P., Buckle, A., Sandhu, S. & Sood, S. Mortality due to immunotherapy related hepatitis. J. Hepatol. 69 , 976–978 (2018).

Lameire, N. H., Flombaum, C. D., Moreau, D. & Ronco, C. Acute renal failure in cancer patients. Ann. Med. 37 , 13–25 (2005).

Ries, F. & Klastersky, J. Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity. Am. J. Kidney Dis. 8 , 368–379 (1986).

Wong, J. L. & Evans, S. E. Bacterial pneumonia in patients with cancer: novel risk factors and management. Clin. Chest Med. 38 , 263–277 (2017).

Lee, L. Y. W. et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet 395 , 1919–1926 (2020).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Williamson, E. J. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 584 , 430–436 (2020). This study used a platform of 17.4 million pseudo-anonymized health-care records to determine risk factors for COVID-19.

Pelosof, L. C. & Gerber, D. E. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin. Proc. 85 , 838–854 (2010).

Donovan, P. J. et al. PTHrP-mediated hypercalcemia: causes and survival in 138 patients. J. Clin. Endocrinol. Metab. 100 , 2024–2029 (2015).

Burtis, W. J. et al. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N. Engl. J. Med. 322 , 1106–1112 (1990). First study to show that patients with cancer-associated hypercalcaemia had elevated concentrations of plasma parathyroid hormone-related protein .

Ellison, D. H. & Berl, T. The syndrome of inappropriate antidiuresis. N. Engl. J. Med. 356 , 2064–2072 (2007).

Okabayashi, T. et al. Diagnosis and management of insulinoma. World J. Gastroenterol. 19 , 829–837 (2013).

Giometto, B. et al. Paraneoplastic neurologic syndrome in the PNS Euronetwork database: a European study from 20 centers. Arch. Neurol. 67 , 330–335 (2010).

Wang, D. Y. et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 4 , 1721 (2018).

Feng, S. et al. Pembrolizumab-induced encephalopathy: a review of neurological toxicities with immune checkpoint inhibitors. J. Thorac. Oncol. 12 , 1626–1635 (2017).

Coustal, C. et al. Prognosis of immune checkpoint inhibitors-induced myocarditis: a case series. J. Immunother. Cancer 11 , e004792 (2023).

Kuderer, N. M., Dale, D. C., Crawford, J., Cosler, L. E. & Lyman, G. H. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106 , 2258–2266 (2006).

Agarwal, M. A. et al. Ventricular arrhythmia in cancer patients: mechanisms, treatment strategies and future avenues. Arrhythm. Electrophysiol. Rev . 12 , e16 (2023).

Zafar, A. et al. The incidence, risk factors, and outcomes with 5-fluorouracil-associated coronary vasospasm. JACC CardioOncol. 3 , 101–109 (2021).

Polk, A. et al. Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity: a retrospective study of 452 consecutive patients with metastatic breast cancer. BMJ Open 6 , e012798 (2016).

Safdar, A., Bodey, G. & Armstrong, D. Infections in patients with cancer: overview. Princip. Pract. Cancer Infect. Dis. https://doi.org/10.1007/978-1-60761-644-3_1 (2011).

Foster, D. S., Jones, R. E., Ransom, R. C., Longaker, M. T. & Norton, J. A. The evolving relationship of wound healing and tumor stroma. JCI Insight 3 , e99911 (2018).

Park, S. J. & Bejar, R. Clonal hematopoiesis in cancer. Exp. Hematol. 83 , 105 (2020).

Liebman, H. A. Thrombocytopenia in cancer patients. Thromb. Res. https://doi.org/10.1016/S0049-3848(14)50011-4 (2014).

Chakraborty, R. et al. Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma. Br. J. Haematol. 189 , 1074–1082 (2020).

Allen, B. M. et al. Systemic dysfunction and plasticity of the immune macroenvironment in cancer models. Nat. Med. 26 , 1125–1134 (2020).

Munn, D. H. & Bronte, V. Immune suppressive mechanisms in the tumor microenvironment. Curr. Opin. Immunol. 39 , 1–6 (2016).

Kochar, R. & Banerjee, S. Infections of the biliary tract. Gastrointest. Endosc. Clin. N. Am. 23 , 199–218 (2013).

Valvani, A., Martin, A., Devarajan, A. & Chandy, D. Postobstructive pneumonia in lung cancer. Ann. Transl. Med. 7 , 357–357 (2019).

Rolston, K. V. I. Infections in cancer patients with solid tumors: a review. Infect. Dis. Ther. 6 , 69–83 (2017).

Wu, X. et al. The association between major complications of immobility during hospitalization and quality of life among bedridden patients: a 3 month prospective multi-center study. PLoS One 13 , e0205729 (2018).

The clinicopathological and prognostic role of thrombocytosis in patients with cancer: a meta-analysis. Oncol. Lett . 13 , 5002–5008 (2017).

Kasthuri, R. S., Taubman, M. B. & Mackman, N. Role of tissue factor in cancer. J. Clin. Oncol. 27 , 4834 (2009).

Wade, J. C. Viral infections in patients with hematological malignancies. Hematology 2006 , 368–374 (2006).

Article   Google Scholar  

Ersvaer, E., Liseth, K., Skavland, J., Gjertsen, B. T. & Bruserud, Ø. Intensive chemotherapy for acute myeloid leukemia differentially affects circulating TC1, TH1, TH17 and TREG cells. BMC Immunol. 11 , 1–12 (2010).

Kuter, D. J. Treatment of chemotherapy-induced thrombocytopenia in patients with non-hematologic malignancies. Haematologica 107 , 1243 (2022).

Rodgers, G. M. et al. Cancer- and chemotherapy-induced anemia. J. Natl Compr. Canc. Netw. 10 , 628–653 (2012).

Nesher, L. & Rolston, K. V. I. The current spectrum of infection in cancer patients with chemotherapy related neutropenia. Infection 42 , 5–13 (2014).

Blijlevens, N. M. A., Logan, R. M. & Netea, M. G. Mucositis: from febrile neutropenia to febrile mucositis. J. Antimicrob. Chemother. 63 , i36–i40 (2009).

Petrelli, F. et al. Association of steroid use with survival in solid tumours. Eur. J. Cancer 141 , 105–114 (2020).

Bolton, K. L. et al. Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nat. Genet. 52 , 1219–1226 (2020). This study identified the molecular characteristics of clonal haematopoiesis that increased risk of therapy-related myeloid neoplasms, with different characteristics associated with different treatment exposures.

Bhatia, R. et al. Do cancer and cancer treatments accelerate aging? Curr. Oncol. Rep. 24 , 1401 (2022).

Eisenstein, T. K. The role of opioid receptors in immune system function. Front. Immunol. 10 , 485158 (2019).

Böll, B. et al. Central venous catheter-related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann. Hematol. 100 , 239 (2021).

Ruiz-Giardin, J. M. et al. Blood stream infections associated with central and peripheral venous catheters. BMC Infect. Dis. 19 , 1–9 (2019).

Lee, D. W. et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124 , 188–195 (2014).

Brahmer, J. R. et al. Safety profile of pembrolizumab monotherapy based on an aggregate safety evaluation of 8937 patients. Eur. J. Cancer 199 , 113530 (2024). Analysis of the toxicity profile of anti-PD1 therapy in more than 8,000 patients.

Larkin, J. et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N. Engl. J. Med. 381 , 1535–1546 (2019).

Vozy, A. et al. Increased reporting of fatal hepatitis associated with immune checkpoint inhibitors. Eur. J. Cancer 123 , 112–115 (2019).

Palaskas, N., Lopez-Mattei, J., Durand, J. B., Iliescu, C. & Deswal, A. Immune checkpoint inhibitor myocarditis: pathophysiological characteristics, diagnosis, and treatment. J. Am. Heart Assoc. 9 , e013757 (2020).

Janssen, J. B. E. et al. Immune checkpoint inhibitor-related Guillain–Barré syndrome: a case series and review of the literature. J. Immunother. 44 , 276–282 (2021).

Camelliti, S. et al. Mechanisms of hyperprogressive disease after immune checkpoint inhibitor therapy: what we (don’t) know. J. Exp. Clin. Cancer Res. 39 , 236 (2020).

Kitamura, W. et al. Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T-cell therapy. Br. J. Haematol. 202 , 294–307 (2023).

Seano, G. et al. Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium. Nat. Biomed. Eng. 3 , 230 (2019).

Madhusoodanan, S., Ting, M. B., Farah, T. & Ugur, U. Psychiatric aspects of brain tumors: a review. World J. Psychiatry 5 , 273 (2015).

Gerstenecker, A. et al. Cognition in patients with newly diagnosed brain metastasis: profiles and implications. J. Neurooncol. 120 , 179 (2014).

Krishna, S. et al. Glioblastoma remodelling of human neural circuits decreases survival. Nature 617 , 599–607 (2023). This study demonstrated that high-grade gliomas remodel neural circuits in the human brain, which promotes tumour progression and impairs cognition.

Taylor, K. R. et al. Glioma synapses recruit mechanisms of adaptive plasticity. Nature 623 , 366–374 (2023). This study showed that brain-derived neurotrophic factor (BDNF)–tropomyosin-related kinase B (TRKB) signalling promotes malignant synaptic plasticity and augments tumour progression.

Hanahan, D. & Monje, M. Cancer hallmarks intersect with neuroscience in the tumor microenvironment. Cancer Cell 41 , 573–580 (2023).

Ahles, T. A. & Root, J. C. Cognitive effects of cancer and cancer treatments. Annu. Rev. Clin. Psychol . 14 , 425–451 (2018).

Allexandre, D. et al. EEG correlates of central origin of cancer-related fatigue. Neural Plast. 2020 , 8812984 (2020).

Büttner-Teleagă, A., Kim, Y. T., Osel, T. & Richter, K. Sleep disorders in cancer — a systematic review. Int. J. Environ. Res. Public Health 18 , 11696 (2021).

Walsh, D. & Nelson, K. A. Autonomic nervous system dysfunction in advanced cancer. Support. Care Cancer 10 , 523–528 (2002).

Ghandour, F. et al. Presenting psychiatric and neurological symptoms and signs of brain tumors before diagnosis: a systematic review. Brain Sci. 11 , 1–20 (2021).

Akechi, T. et al. Somatic symptoms for diagnosing major depression in cancer patients. Psychosomatics 44 , 244–248 (2003).

Nho, J. H., Kim, S. R. & Kwon, Y. S. Depression and appetite: predictors of malnutrition in gynecologic cancer. Support. Care Cancer 22 , 3081–3088 (2014).

Thaker, P. H. et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat. Med. 12 , 939–944 (2006). This study linked chronic behavioural stress to higher levels of tissue catecholamines and tumour angiogenesis, resulting in greater tumor burden and invasion in ovarian cancer.

Chang, A. et al. Beta-blockade enhances anthracycline control of metastasis in triple-negative breast cancer. Sci. Transl. Med . 15 , eadf1147 (2023).

Magnon, C. et al. Autonomic nerve development contributes to prostate cancer progression. Science 341 , 1236361 (2013). This study showed that the formation of autonomic nerve fibres in the prostate gland regulates prostate cancer development and dissemination in mouse models.

Baracos, V. E., Martin, L., Korc, M., Guttridge, D. C. & Fearon, K. C. H. Cancer-associated cachexia. Nat. Rev. Dis. Prim. 4 , 17105 (2018).

Fearon, K. et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 12 , 489–495 (2011). International consensus definitions of cancer cachexia.

Bossi, P., Delrio, P., Mascheroni, A. & Zanetti, M. The spectrum of malnutrition/cachexia/sarcopenia in oncology according to different cancer types and settings: a narrative review. Nutrients 13 , 1980 (2021).

Farkas, J. et al. Cachexia as a major public health problem: frequent, costly, and deadly. J. Cachexia Sarcopenia Muscle 4 , 173–178 (2013).

Dennison, E. M., Sayer, A. A. & Cooper, C. Epidemiology of sarcopenia and insight into possible therapeutic targets. Nat. Rev. Rheumatol. 13 , 340–347 (2017).

Farasat, M. et al. Long-term cardiac arrhythmia and chronotropic evaluation in patients with severe anorexia nervosa (LACE-AN): a pilot study. J. Cardiovasc. Electrophysiol. 31 , 432–439 (2020).

Mehler, P. S., Anderson, K., Bauschka, M., Cost, J. & Farooq, A. Emergency room presentations of people with anorexia nervosa. J. Eat. Disord. 11 , 16 (2023).

Ferrer, M. et al. Cachexia: a systemic consequence of progressive, unresolved disease. Cell 186 , 1824–1845 (2023).

Bourke, C. D., Berkley, J. A. & Prendergast, A. J. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol. 37 , 386–398 (2016).

Tisdale, M. J. Biology of cachexia. J. Natl Cancer Inst. 89 , 1763–1773 (1997).

Babic, A. et al. Adipose tissue and skeletal muscle wasting precede clinical diagnosis of pancreatic cancer. Nat. Commun. 14 , 4754 (2023).

Waning, D. L. et al. Excess TGF-β mediates muscle weakness associated with bone metastases in mice. Nat. Med. 21 , 1262 (2015). This study showed that bone metastases cause TGFβ to be released from the bone marrow, resulting in leakage of calcium from skeletal muscle cells contributing to muscle weakness.

Greco, S. H. et al. TGF-β blockade reduces mortality and metabolic changes in a validated murine model of pancreatic cancer cachexia. PLoS ONE 10 , e0132786 (2015).

Johnen, H. et al. Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. Nat. Med. 13 , 1333–1340 (2007). This study showed that GDF15 was elevated in patients with cancer-associated weight loss and that this was a central regulator of appetite and therefore a potential therapeutic target.

Al-Sawaf, O. et al. Body composition and lung cancer-associated cachexia in TRACERx. Nat. Med. 29 , 846–858 (2023). This study showed an association among lower skeletal muscle area, subcutaneous adipose tissue and visceral adipose tissue and decreased survival in patients with non-small-cell lung cancer and these were associated with higher levels of circulating GDF15.

Ahmed, D. S., Isnard, S., Lin, J., Routy, B. & Routy, J. P. GDF15/GFRAL pathway as a metabolic signature for cachexia in patients with cancer. J. Cancer 12 , 1125–1132 (2021).

Rebbapragada, A., Benchabane, H., Wrana, J. L., Celeste, A. J. & Attisano, L. Myostatin signals through a transforming growth factor β-like signaling pathway to block adipogenesis. Mol. Cell. Biol. 23 , 7230 (2003).

Queiroz, A. L. et al. Blocking ActRIIB and restoring appetite reverses cachexia and improves survival in mice with lung cancer. Nat. Commun. 13 , 1–17 (2022).

Loumaye, A. et al. Role of activin A and myostatin in human cancer cachexia. J. Clin. Endocrinol. Metab. 100 , 2030–2038 (2015).

Barton, B. E. & Murphy, T. F. Cancer cachexia is mediated in part by the induction of IL-6-like cytokines from the spleen. Cytokine 16 , 251–257 (2001).

Webster, J. M., Kempen, L. J. A. P., Hardy, R. S. & Langen, R. C. J. Inflammation and skeletal muscle wasting during cachexia. Front. Physiol. 11 , 597675 (2020).

Strassmann, G., Masui, Y., Chizzonite, R. & Fong, M. Mechanisms of experimental cancer cachexia local involvement of 11-1 in colon-26 tumor. J. Immunol. 150 , 2341–2345 (1993).

Stovroff, M. C., Fraker, D. L., Swedenborg, J. A. & Norton, J. A. Cachectin/tumor necrosis factor: a possible mediator of cancer anorexia in the rat. Cancer Res. 48 , 4567–4572 (1988).

CAS   PubMed   Google Scholar  

Wyke, S. M. & Tisdale, M. J. NF-κB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin–proteasome system in skeletal muscle. Br. J. Cancer 92 , 711 (2005).

Cai, D. et al. IKKβ/NF-κB activation causes severe muscle wasting in mice. Cell 119 , 285–298 (2004). This study showed that activation of NF-κB, through muscle-specific transgenic expression of activated inhibitor of NF-κB kinase subunit β (IKKβ), causes profound muscle wasting in mice.

Patel, H. J. & Patel, B. M. TNF-α and cancer cachexia: molecular insights and clinical implications. Life Sci. 170 , 56–63 (2017).

Mergenthaler, P., Lindauer, U., Dienel, G. A. & Meisel, A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci. 36 , 587 (2013).

Sillos, E. M. et al. Lactic acidosis: a metabolic complication of hematologic malignancies case report and review of the literature. Cancer 92 , 2237–46 (2000).

Rampello, E., Fricia, T. & Malaguarnera, M. The management of tumor lysis syndrome. Nat. Clin. Pract. Oncol. 3 , 438–447 (2006).

Delano, M. J. & Moldawer, L. L. The origins of cachexia in acute and chronic inflammatory diseases. Nutr. Clin. Pract. 21 , 68–81 (2006).

Lombardi, A., Villa, S., Castelli, V., Bandera, A. & Gori, A. T-cell exhaustion in Mycobacterium tuberculosis and nontuberculous mycobacteria infection: pathophysiology and therapeutic perspectives. Microorganisms 9 , 2460 (2021).

Moldawer, L. L. & Sattler, F. R. Human immunodeficiency virus-associated wasting and mechanisms of cachexia associated with inflammation. Semin. Oncol. 25 , 73–81 (1998).

von Kobbe, C. Targeting senescent cells: approaches, opportunities, challenges. Aging 11 , 12844 (2019).

Shafqat, S., Chicas, E. A., Shafqat, A. & Hashmi, S. K. The Achilles’ heel of cancer survivors: fundamentals of accelerated cellular senescence. J. Clin. Invest. 132 , e158452 (2022).

Wang, L., Lankhorst, L. & Bernards, R. Exploiting senescence for the treatment of cancer. Nat. Rev. Cancer 22 , 340–355 (2022).

Terry, W., Olson, L. G., Ravenscroft, P., Wilss, L. & Boulton-Lewis, G. Hospice patients’ views on research in palliative care. Intern. Med. J. 36 , 406–413 (2006).

White, C. & Hardy, J. What do palliative care patients and their relatives think about research in palliative care? A systematic review. Support. Care Cancer 18 , 905–911 (2010).

Foster, B., Bagci, U., Mansoor, A., Xu, Z. & Mollura, D. J. A review on segmentation of positron emission tomography images. Comput. Biol. Med. 50 , 76–96 (2014).

Bera, K., Braman, N., Gupta, A., Velcheti, V. & Madabhushi, A. Predicting cancer outcomes with radiomics and artificial intelligence in radiology. Nat. Rev. Clin. Oncol. 19 , 132–146 (2022).

Kaczanowska, S. et al. Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy. Cancer Cell 42 , 35–51.e8 (2024).

Dutta, S. & Sengupta, P. Men and mice: relating their ages. Life Sci. 152 , 244–248 (2016).

Alpert, A. et al. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nat. Med. 25 , 487–495 (2019).

Gyawali, B., Hey, S. P. & Kesselheim, A. S. Evaluating the evidence behind the surrogate measures included in the FDA’s table of surrogate endpoints as supporting approval of cancer drugs. eClinicalMedicine 21 , 100332 (2020).

Hong, W. et al. Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning. Proc. Natl Acad. Sci. USA 112 , E5351–E5360 (2015).

Johnson, D. E., O’Keefe, R. A. & Grandis, J. R. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat. Rev. Clin. Oncol. 15 , 234–248 (2018).

Bowden, M. B. et al. Demographic and clinical factors associated with suicide in gastric cancer in the United States. J. Gastrointest. Oncol. 8 , 897–901 (2017).

Zaorsky, N. G. et al. Suicide among cancer patients. Nat. Commun. 10 , 1–7 (2019).

CAS   Google Scholar  

Hu, X. et al. Suicide risk among individuals diagnosed with cancer in the US, 2000 – 2016 . JAMA Netw. Open 6 , e2251863 (2023).

Google Scholar  

Abdel-Rahman, O. Socioeconomic predictors of suicide risk among cancer patients in the United States: a population-based study. Cancer Epidemiol. 63 , 101601 (2019).

Pinquart, M. & Duberstein, P. R. Depression and cancer mortality: a meta-analysis. Psychol. Med. 40 , 1797–1810 (2010).

Fitzgerald, P. et al. The relationship between depression and physical symptom burden in advanced cancer. BMJ Support. Palliat. Care 5 , 381–388 (2015).

Chida, Y., Hamer, M., Wardle, J. & Steptoe, A. Do stress-related psychosocial factors contribute to cancer incidence and survival? Nat. Clin. Pract. Oncol. 5 , 466–475 (2008).

He, X. Y. et al. Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment. Cancer Cell 42 , 474–486.e12 (2024). This study found that chronic stress shifts the normal circadian rhythm of neutrophils resulting in increased neutrophil extracellular trap (NET) formation via glucocorticoid release, resulting in a metastasis-promoting microenvironment.

Fann, J. R., Ell, K. & Sharpe, M. Integrating psychosocial care into cancer services. J. Clin. Oncol. 30 , 1178–1186 (2012).

Jacobsen, P. B. & Wagner, L. I. A new quality standard: the integration of psychosocial care into routine cancer care. J. Clin. Oncol. 30 , 1154–1159 (2012).

Gorin, S. S. et al. Meta-analysis of psychosocial interventions to reduce pain in patients with cancer. J. Clin. Oncol. 30 , 539–547 (2012).

Li, M. et al. Systematic review and meta-analysis of collaborative care interventions for depression in patients with cancer. Psychooncology 26 , 573–587 (2017).

Bova, G. S. et al. Optimal molecular profiling of tissue and tissue components: defining the best processing and microdissection methods for biomedical applications. Mol. Biotechnol. 29 , 119–152 (2005).

Gundem, G. et al. The evolutionary history of lethal metastatic prostate cancer. Nature 520 , 353–357 (2015). This study found that metastasis-to-metastasis spread was common in prostate cancer evolution and that lesions affecting tumour suppressor genes occurred as single events, whereas mutations in genes involved in androgen receptor signalling commonly involved multiple, convergent events in different metastases.

Turajlic, S. et al. Tracking cancer evolution reveals constrained routes to metastases: TRACERx renal. Cell 173 , 581–594.e12 (2018). This study examined evolutionary trajectories of 100 renal cancers and found that metastasis competence was driven by chromosome complexity, not by driver mutation load, and that loss of 9p and 14q was a common driver.

Spain, L. et al. Late-stage metastatic melanoma emerges through a diversity of evolutionary pathways. Cancer Discov. 13 , 1364–1385 (2023). This study examined evolutionary trajectories of melanoma metastasis and observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery.

Download references

Acknowledgements

A.B. is funded by National Institutes of Health/National Cancer Institute P30 CA008748 and R01-CA245499. K.B. is employed by the UK National Health Service. T.R.C. acknowledges funding support from the National Health and Medical Research Council (NHMRC) Ideas (2000937), Project (1129766, 1140125), Development (2013881) and Fellowship (1158590) schemes, a Cancer Institute NSW Career Development Fellowship (CDF171105), Cancer Council NSW project support (RG19-09, RG23-11) and Susan G. Komen for the Cure (CCR17483294). T.G. is funded by the Cancer Prevention and Research Institute of Texas Grant 00011633. M.J.-H. has received funding from CRUK, NIH National Cancer Institute, IASLC International Lung Cancer Foundation, Lung Cancer Research Foundation, Rosetrees Trust, UKI NETs and NIHR. T.J. acknowledges funding from Cancer Grand Challenges (NIH: 1OT2CA278690-01; CRUK: CGCATF-2021/100019), the Mark Foundation for Cancer Research (20-028-EDV), the Osprey Foundation, Fortune Footwear, Cold Spring Harbour Laboratory (CSHL) and developmental funds from CSHL Cancer Center Support Grant 5P30CA045508. R.K. is funded by the Intramural Research Program, the National Cancer Institute, NIH Clinical Center and the National Institutes of Health (NIH NCI ZIABC011332-06 and NIH NCI ZIABC011334-10). R.L. is supported by a Wellcome Early Career Investigator Award (225724/Z/22/Z). E.S. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2040), the UK Medical Research Council (CC2040) and the Wellcome Trust (CC2040) and the European Research Council (ERC Advanced Grant CAN_ORGANISE, Grant agreement number 101019366). E.S. reports personal grants from Mark Foundation and the European Research Council. C.S. is a Royal Society Napier Research Professor (RSRP\R\210001). His work is supported by the Francis Crick Institute that receives its core funding from Cancer Research UK (CC2041), the UK Medical Research Council (CC2041) and the Wellcome Trust (CC2041) and the European Research Council under the European Union’s Horizon 2020 research and innovation programme (ERC Advanced Grant PROTEUS Grant agreement number 835297). M.G.V.H. reports support from the Lustgarten Foundation, the MIT Center for Precision Cancer Medicine, the Ludwig Center at MIT and NIH grants R35 CA242379 and P30 CA1405141.

Author information

These authors contributed equally: Adrienne Boire, Katy Burke, Thomas R. Cox, Theresa Guise, Mariam Jamal-Hanjani, Tobias Janowitz, Rosandra Kaplan, Rebecca Lee, Charles Swanton, Matthew G. Vander Heiden, Erik Sahai.

Authors and Affiliations

Memorial Sloan Kettering Cancer Center, New York, NY, USA

Adrienne Boire

University College London Hospitals NHS Foundation Trust and Central and North West London NHS Foundation Trust Palliative Care Team, London, UK

Cancer Ecosystems Program, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia

Thomas R. Cox

School of Clinical Medicine, St Vincent’s Healthcare Clinical Campus, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia

Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Theresa Guise

Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK

Mariam Jamal-Hanjani

Department of Oncology, University College London Hospitals, London, UK

Mariam Jamal-Hanjani & Charles Swanton

Cancer Research UK Lung Centre of Excellence, University College London Cancer Institute, London, UK

Cold Spring Harbour Laboratory, Cold Spring Harbour, New York, NY, USA

Tobias Janowitz

Northwell Health Cancer Institute, New York, NY, USA

Paediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Rosandra Kaplan

Tumour Cell Biology Laboratory, The Francis Crick Institute, London, UK

Rebecca Lee & Erik Sahai

Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

Rebecca Lee

Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK

Charles Swanton

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

Matthew G. Vander Heiden

Dana-Farber Cancer Institute, Boston, MA, USA

You can also search for this author in PubMed   Google Scholar

Contributions

All authors researched data for the article. A.B., K.B., T.R.C., T.G., T.J., C.S., M.G.V.H, R.K., M.J.-H. and E.S. contributed substantially to discussion of the content. T.C., R.L. and E.S. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Corresponding authors

Correspondence to Thomas R. Cox or Erik Sahai .

Ethics declarations

Competing interests.

A.B. is an inventor on pending patents 63/449,817, 63/052,139 as well as awarded patents 11,305,014 and 10,413,522; all issued to the Sloan Kettering Institute. She has received personal fees from Apelis Pharmaceuticals and serves as an unpaid member of the Evren Technologies SAB. K.B., T.R.C., T.G., T.J. and R.K. declare no competing interests. M.J.-H. reports support from Achilles Therapeutics Scientific Advisory Board and Steering Committee, Pfizer, Astex Pharmaceuticals, Oslo Cancer Cluster and Bristol Myers Squibb outside the submitted work. R.L. reports personal fees from Pierre Fabre and has research funding from BMS, Astra Zeneca and Pierre Fabre outside the submitted work. E.S. reports grants from Novartis, Merck Sharp Dohme, AstraZeneca and personal fees from Phenomic outside the submitted work. C.S. reports grants and personal fees from Bristol Myers Squibb, AstraZeneca, Boehringer-Ingelheim, Roche-Ventana, personal fees from Pfizer, grants from Ono Pharmaceutical, Personalis, grants, personal fees and other support from GRAIL, other support from AstraZeneca and GRAIL, personal fees and other support from Achilles Therapeutics, Bicycle Therapeutics, personal fees from Genentech, Medixci, China Innovation Centre of Roche (CiCoR) formerly Roche Innovation Centre, Metabomed, Relay Therapeutics, Saga Diagnostics, Sarah Canon Research Institute, Amgen, GlaxoSmithKline, Illumina, MSD, Novartis, other support from Apogen Biotechnologies and Epic Bioscience outside the submitted work; in addition, C.S. has a patent for PCT/US2017/028013 licensed to Natera Inc., UCL Business, a patent for PCT/EP2016/059401 licensed to Cancer Research Technology, a patent for PCT/EP2016/071471 issued to Cancer Research Technology, a patent for PCT/GB2018/051912 pending, a patent for PCT/GB2018/052004 issued to Francis Crick Institute, University College London, Cancer Research Technology Ltd, a patent for PCT/GB2020/050221 issued to Francis Crick Institute, University College London, a patent for PCT/EP2022/077987 pending to Cancer Research Technology, a patent for PCT/GB2017/053289 licensed, a patent for PCT/EP2022/077987 pending to Francis Crick Institute, a patent for PCT/EP2023/059039 pending to Francis Crick Institute and a patent for PCT/GB2018/051892 pending to Francis Crick Institute. C.S. is Co-chief Investigator of the NHS Galleri trial funded by GRAIL. He is Chief Investigator for the AstraZeneca MeRmaiD I and II clinical trials and Chair of the Steering Committee. C.S. is cofounder of Achilles Therapeutics and holds stock options. M.G.V.H. is a scientific adviser for Agios Pharmaceuticals, iTeos Therapeutics, Sage Therapeutics, Faeth Therapeutics, Droia Ventures and Auron Therapeutics on topics unrelated to the presented work.

Peer review

Peer review information.

Nature Reviews Cancer thanks Vickie Baracos, Clare M. Isacke, who co-reviewed with Amanda Fitzpatrick and Erica Sloan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

An autoimmune encephalitis characterized by complex neuropsychiatric features and the presence of immunoglobulin G (IgG) antibodies against the NR1 subunit of the NMDA receptors in the central nervous system.

Partial collapse or incomplete inflation of the lung.

Pressure-induced movement of brain tissue.

An ageing-associated process in which haematopoiesis becomes dominated by one or a small number of genetically distinct stem or progenitor cells. Clonal haematopoiesis is linked to an increased risk of haematological malignancies.

Inability of the heart to pump blood properly.

Constriction of the arteries that supply blood to the heart.

(CRH). One of the major factors that drives the response of the body to stress.

(DIC). A rare but serious condition in which abnormal blood clotting occurs throughout the blood vessels of the body.

Inflammation of the brain.

An abnormal connection that forms between two body parts, such as an organ or blood vessel and another often unrelated structure in close proximity.

A rare disorder in which the immune system of a body attacks the nerves, which can lead to paralysis.

The stopping of flow of blood, typically associated with the bodies response to prevent and stop bleeding.

A build-up of fluid within the cavities of the brain.

Elevated calcium levels in the blood, often caused by overactive parathyroid glands. Hypercalcaemia is linked to kidney stones, weakened bones, altered digestion and potentially altered cardiac and brain function.

(HPD). Rapid tumour progression sometimes observed during immune checkpoint inhibitor treatment.

The condition that occurs when the level of sodium in the blood is low.

Harm, which is often unavoidable, caused by cancer treatments.

The marked suppression of polyclonal immunoglobulins in the body.

(LEMS). A neuromuscular junction disorder affecting communication between nerves and muscles, which manifests as a result of a paraneoplastic syndrome or a primary autoimmune disorder. Many cases are associated with small-cell lung cancer.

When cancer cells spread to the tissue layers covering the brain and spinal cord (the leptomeninges).

Also known as pulmonary oedema is a condition caused by excess fluid in the lungs. This fluid collects in the alveoli compromising function and making it difficult to breathe.

The observation of displacement of brain tissue across the centre line of the brain, suggestive of uneven intracranial pressure.

Decreased blood flow to the myocardium, commonly called a heart attack.

Inflammation specifically of the middle layer of the heart wall.

A group of rare disorders that occur when the immune system reacts to changes in the body triggered by the presence of a neoplasm.

A dense network of nerves that transmit information from the brain (efferent neurons) to the periphery and conversely transmit information from the periphery to the brain (afferent neurons). A component of the peripheral nervous system is the autonomic nervous system.

A build-up of fluid between the tissues that line the lungs and the chest wall.

A condition characterized by loss of skeletal muscle mass and function.

The lodging of a circulating blood clot within a vessel leading to obstruction. Thromboembolisms may occur in veins (venous thromboembolism) and arteries (arterial thromboembolism).

A key component of the pathway regulating blood clotting, specifically the receptor and cofactor for factor VII/VIIa.

A syndrome occurs when tumour cells release their contents into the bloodstream, either spontaneously or more typically, in response to therapeutic intervention.

Devices worn on the body, typically in the form of accessories or clothing, that incorporate advanced electronics and technology to monitor, track or enhance various aspects of human life. Examples include smartwatches and fitness trackers.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Cite this article.

Boire, A., Burke, K., Cox, T.R. et al. Why do patients with cancer die?. Nat Rev Cancer 24 , 578–589 (2024). https://doi.org/10.1038/s41568-024-00708-4

Download citation

Accepted : 15 May 2024

Published : 19 June 2024

Issue Date : August 2024

DOI : https://doi.org/10.1038/s41568-024-00708-4

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

This article is cited by

The road less travelled.

Nature Reviews Cancer (2024)

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.