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Center for Childhood Cancer Research

The Center for Childhood Cancer Research represents a highly integrated basic, translational and clinical research environment dedicated to eradicating the pain and suffering caused by cancer in children.

Research Topics

The work of our investigators touches every type of childhood cancer. Through our research, we're finding ways to improve quality of life for cancer survivors.

Adolescent and Young Adult Oncology Research

Researchers are developing and clinically validating psychosocial assessment tools and mHealth intervention strategies to improve medical, developmental and psychological outcomes for AYA cancer patients and their families.

Cancer Genetics Research

Research into cancer genetics and genomics can help improve cancer diagnosis and aid in the development of new therapies for children with cancer.

Cancer Predisposition Research

Researchers are using the latest advances in oncology, molecular biology and genomic analyses to provide care and counseling to children with genetic predispositions to cancer.

Developmental Therapeutics

Investigators are quickly translating basic research discoveries into promising new treatment options for children with cancer.

Hematologic Malignancies Research

Modern molecular and immunological approaches are being applied to develop and optimize treatments for infants and children with hematologic malignancies.

Neuro-oncology Research

Investigators at the Center for Childhood Cancer Research are using genomic, immunotherapeutic and targeted cancer therapy approaches to develop new treatments for children with spinal cord and brain tumors.

Neuroblastoma Research

Researchers are developing new treatment regimens and optimizing those that already exist to treat infants and children with neuroblastoma.

Solid Tumor Research

Investigators at the Center for Childhood Cancer Research are developing and clinically evaluating new treatment options for children with solid tumors, including targeted cancer agents and immunotherapies.

Behavioral Oncology Research

Investigators are applying behavioral translational research to improve psychosocial outcomes and quality of life for children and adolescents with cancer.

Cancer Pathobiology Research

Cancer pathobiology is an integrative discipline seeking insights into molecular and cellular mechanisms responsible for all aspects of cancerous growth.

Cancer Survivorship Research

Investigators at the Center for Childhood Cancer Research are developing programs and interventional strategies to identify, treat and manage therapy-related late effects experienced by survivors of childhood cancer and their families.

Fertility Preservation Research

Researchers at the Center for Childhood Cancer Research have developed fertility preservations options for male and female children who may be at risk for impaired or lost fertility after cancer treatment.

Langerhans Cell Histiocytosis Research

Researchers are using molecular biological and immunotherapeutic approaches to better define the relationship between LCH and cancer and to develop new safe and effective treatment options for children with LCH.

Neuroblastoma Developmental Therapeutics

Investigators at the Center for Childhood Cancer Research are catalyzing the incorporation of research advancements into routine clinical care for children with relapsed or refractory neuroblastoma.

Retinoblastoma Research

Researchers are using modern clinical and technological approaches to improve existing treatment regimens and develop new or alternative therapies to treat children with retinoblastoma.

Thyroid Cancer Research

Researchers are using both clinical and basic science approaches to improve the diagnosis, treatment and health of children with thyroid cancer.

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Paediatric cancer articles within Nature Medicine

Article 11 April 2024 | Open Access

Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers

In an observational study evaluating functional precision medicine in children and adolescents with relapsed or refractory solid and hematologic malignancies, it was feasible to provide personalized treatment recommendations to treating physicians on the basis of genomic profiling and ex vivo drug sensitivity testing within 4 weeks.

• Arlet M. Acanda De La Rocha
• , Noah E. Berlow
•  &  Diana J. Azzam

Article | 07 March 2024

Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors

An observational study reports the joint effects of polygenic risk scores and radiation treatment exposure with a subsequent increased risk of multiple solid cancers in two large cohorts of survivors of childhood cancer.

• Todd M. Gibson
• , Danielle M. Karyadi
•  &  Lindsay M. Morton

Article 17 November 2023 | Open Access

The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

In a phase 2 trial, the oral type II RAF inhibitor tovorafenib exhibited an overall response rate of 67% in patients with BRAF -altered relapsed/refractory pediatric low-grade glioma.

• Lindsay B. Kilburn
• , Dong-Anh Khuong-Quang
•  &  Karsten Nysom

Article 11 September 2023 | Open Access

Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer

In a pooled analysis of six international studies involving about 17,900 female survivors of childhood cancer, the use of doxorubicin was associated with a dose-dependent risk of subsequent breast cancer, irrespective of prior chest radiotherapy exposure.

• Yuehan Wang
• , Cécile M. Ronckers
•  &  Jeanette F. Winther

Article 06 July 2023 | Open Access

Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia

In children with relapsed or refractory B cell acute lymphoblastic leukemia and in complete remission after CD19 CAR-T cell therapy, long-lived CAR-T cells express a persistence gene signature that is also present in persistent CD19 CAR-T cells from adults with chronic lymphocytic leukemia.

• Nathaniel D. Anderson
• , Jack Birch
•  &  Sara Ghorashian

Consensus Statement | 15 June 2023

A joint international consensus statement for measuring quality of survival for patients with childhood cancer

The International Childhood Cancer Outcome Project group, involving survivors and other relevant stakeholders, develop a set of core outcomes to measure the quality of care for 17 types of childhood cancers.

• Rebecca J. van Kalsbeek
• , Melissa M. Hudson
•  &  Lisa Zwiers

Article | 15 May 2023

Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results

In updated results from a phase 1 trial of GD2-specific CAR-NKT cells in patients with neuroblastoma, no dose-limiting toxicities were observed across multiple dose levels; the maximum tolerated dose was not reached; and there was evidence of anti-tumor activity.

• Andras Heczey
•  &  Leonid S. Metelitsa

Article 03 April 2023 | Open Access

Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results

In children, adolescents and adults with mutated ALK-driven relapsed or refractory neuroblastoma, a third-generation ALK inhibitor with or without chemotherapy was well tolerated, and recommended phase 2 doses were successfully identified in all patient groups.

• Kelly C. Goldsmith
• , Julie R. Park
•  &  Yael P. Mossé

News & Views | 17 March 2023

Accurate diagnosis of pediatric brain cancers

Integrative approaches continue to improve diagnostic accuracy for pediatric brain cancers, but much more is needed from researchers, governments and regulators if precision medicine with curative treatments are to become a reality.

• Pratiti Bandopadhayay
•  &  Elaine R. Mardis

Article 17 March 2023 | Open Access

Diagnostic classification of childhood cancer using multiscale transcriptomics

A new multilevel clustering approach applied retrospectively to 13,000 transcriptomes of different tumors reveals a new diagnostic classification of childhood cancers, in some cases allowing a better prediction of disease outcomes.

• Federico Comitani
• , Joshua O. Nash
•  &  Adam Shlien

Article 16 March 2023 | Open Access

Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology

The integration of DNA methylation profiling and targeted sequencing with neuropathology improves the diagnostic accuracy of central nervous system tumors in a population-based cohort of more than 1,200 newly diagnosed pediatric patients.

• Dominik Sturm
• , David Capper
•  &  David. T. W. Jones

Article 05 January 2023 | Open Access

Pharmacotypes across the genomic landscape of pediatric acute lymphoblastic leukemia and impact on treatment response

Pharmacotyping analyses of large cohorts of pediatric acute lymphoblastic leukemia identify correlations between drug sensitivities and clinical outcomes across different genomic subtypes.

• Shawn H. R. Lee
• , Wenjian Yang
•  &  Jun J. Yang

News & Views | 08 August 2022

Predicting chronic morbidity in childhood cancer survivors

Incorporating genetic factors into risk models improves the prediction of severe obesity for survivors of childhood cancer, which could promote early interventions and better long-term care.

• Lynda M. Vrooman
•  &  Lisa R. Diller

Article | 23 June 2022

Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer

An interim report from the GAIN/iCat2 study shows that molecular profiling of pediatric solid malignancies clarifies diagnostic classifications and provides opportunities for matched targeted therapy.

• Alanna J. Church
• , Laura B. Corson
•  &  Katherine A. Janeway

World View | 19 April 2022

How to correct the market for children’s cancer drugs

The development of pediatric cancer drugs is vastly underfunded compared with that for adults, but legislation can correct market failures.

• Nancy F. Goodman

Article | 13 January 2022

Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication

The combination of anti-GD2 and CD47 blockade mediates robust anti-tumor activity in mouse models of neuroblastoma, osteosarcoma and small-cell lung cancer by reorienting macrophage activity toward tumor cell phagocytosis.

• Johanna Theruvath
• , Marie Menard
•  &  Robbie G. Majzner

Article 06 January 2022 | Open Access

Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency

Hypermutation and microsatellite burden determine responses and long-term survival following PD-1 blockade in children and young adults with refractory cancers resulting from germline DNA replication repair deficiency.

• Anirban Das
• , Sumedha Sudhaman
•  &  Uri Tabori

Article 12 October 2021 | Open Access

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial

Bicistronic CAR T cells targeting CD19 and CD22 exhibit clinical activity and low toxicity in pediatric and young adult patients with B cell acute lymphoblastic leukemia, with relapses associated with limited CAR T cell persistence.

• Shaun Cordoba
• , Shimobi Onuoha
•  &  Persis J. Amrolia

Article | 12 July 2021

Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis

In an interim analysis of a phase 1 trial, repeated intracranial infusions of HER2-specific CAR T cells were well tolerated with no observed dose-limiting toxicities in three young adult patients with CNS tumors.

• Nicholas A. Vitanza
• , Adam J. Johnson
•  &  Julie R. Park

Article | 13 January 2021

Cabozantinib for neurofibromatosis type 1–related plexiform neurofibromas: a phase 2 trial

Cabozantinib, an inhibitor of multiple receptor tyrosine kinases, has efficacy in a mouse model of neurofibromatosis type I and has clinical activity in reducing plexiform neurofibroma volume in a phase II trial of patients with NF1.

• Michael J. Fisher
• , Chie-Schin Shih
•  &  D. Wade Clapp

News & Views | 19 October 2020

Entering the era of precision medicine in pediatric oncology

The Zero Childhood Cancer Program’s multi-platform sequencing approach identified molecular alterations in 94% of a cohort of 247 pediatric patients with high-risk cancers, which has enabled more-precise diagnoses and alternative therapeutic recommendations.

• Djihad Hadjadj
• , Shriya Deshmukh
•  &  Nada Jabado

Brief Communication | 12 October 2020

Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis

In an interim analysis of a first-in-human phase 1 trial of patients with neuroblastoma, highly pure GD2-specific CAR-NKT cells were well tolerated with no observed dose-limiting toxicities.

• , Amy N. Courtney

Article | 05 October 2020

Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer

The Zero Childhood Cancer pediatric precision medicine program informs treatment recommendations for children with high-risk cancers through comprehensive molecular profiling

• , Chelsea Mayoh
•  &  Mark J. Cowley

Article | 27 April 2020

Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma

Intraventricularly delivered monovalent and trivalent CAR T cells exhibit greater therapeutic efficacy as compared with intravenously delivered CAR T cells in medulloblastoma xenograft mouse models and show potency in ependymoma xenograft mouse models.

• Laura K. Donovan
• , Alberto Delaidelli
•  &  Michael D. Taylor

Letter | 27 April 2020

Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors

CAR T cells administered intracerebroventricularly or intratumorally exhibit more rapid kinetics, reduced systemic toxicity and greater therapeutic potency as compared to intravenously delivered CAR T cells in atypical teratoid/rhabdoid tumor xenograft mouse models.

• , Elena Sotillo
•  &  Crystal L. Mackall

Review Article | 06 March 2019

Developmental origins and emerging therapeutic opportunities for childhood cancer

Childhood cancers are developmentally distinct from adult cancers and arise from cellular reprogramming as a result of epigenetic mutations or gene fusions, providing unique therapeutic opportunities.

• Mariella Filbin
•  &  Michelle Monje

Resource | 22 October 2018

A biobank of patient-derived pediatric brain tumor models

A resource of preclinical pediatric brain tumor models with detailed molecular characterization provides a platform for the community to test novel therapeutic approaches.

• Sebastian Brabetz
• , Sarah E. S. Leary
•  &  James M. Olson

Article | 02 July 2018

Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells

Genomic and functional analysis of intratumor heterogeneity in pediatric glioma uncovers early clonal divergence and stable spontaneous cooperation between subclonal populations throughout tumor evolution.

• , Anna Burford
•  &  Chris Jones

News & Views | 07 May 2018

CAR T cells for childhood diffuse midline gliomas

Anti-GD2 chimeric antigen receptor (CAR)-modified T cells may be a new and innovative approach for the treatment of pediatric H3-K27M-mutant diffuse midline gliomas.

• Vijay Ramaswamy
•  &  Michael D Taylor

News & Views | 01 January 2018

Genomics in childhood acute myeloid leukemia comes of age

A Children's Oncology Group study of nearly 1,000 pediatric acute myeloid leukemia (AML) cases reveals marked differences between the genomic landscapes of pediatric and adult AML and offers directions for future work.

• Andrew M Brunner
•  &  Timothy A Graubert

Resource | 11 December 2017

The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions

A comprehensive molecular analysis of almost 1,000 pediatric subjects with acute myeloid leukemia (AML) uncovers widespread differences in pediatric AML as compared to adult AML, including a higher frequency of structural variants and different mutational patterns and epigenetic signatures. Future studies are needed to characterize the functional relevance of these alterations and to explore age-tailored therapies to improve disease control in younger patients.

• Hamid Bolouri
• , Jason E Farrar
•  &  Soheil Meshinchi

Editorial | 01 September 2017

Children first

Drugs administered to children with cancer were typically developed under the assumption that childhood cancers are similar to their tissue-matched adult counterparts. Focusing on identifying and targeting alterations present specifically in childhood tumors will accelerate the development of tailored therapies and improve the prognosis of children with cancer.

Resource | 30 January 2017

DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma

DNA methylation sequencing and bioinformatic analyses uncover an epigenetic disease spectrum in Ewing sarcoma. These characteristic epigenome patterns correlate with state of differentiation and disease aggressiveness, and pave the way for the development of biomarkers.

• Nathan C Sheffield
• , Gaelle Pierron
•  &  Eleni M Tomazou

News & Views | 07 March 2011

Hunting ALK to feed targeted cancer therapy

Neuroblastoma is a fatal childhood cancer, but lack of knowledge about the underlying causative genes has hampered the development of effective therapies. The identification of anaplastic lymphoma kinase (ALK) mutations as drivers of neuroblastoma has indicated that targeted therapy with ALK inhibitors might be a valuable strategy in the fight against this lethal cancer.

• Anton Wellstein
•  &  Jeffrey A Toretsky

News | 07 March 2011

The search for child cancer drugs grows up

• Branwen Morgan

News & Views | 06 December 2010

Crippling SWI-SNF makes tumors GLI-ful

The chromatin remodeling complex SWI-SNF is altered in cancer. New findings now show that the core component SNF5 can block a Hedgehog (Hh) effector, which promotes malignant rhabdoid tumor growth when SNF5 is lost (pages 1429–1433 ). Targeting this Hh effector may be a way to combat these aggressive childhood tumors.

• Jeremy F Reiter

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Wiemels and de Smith Labs | Children's Cancer Research Laboratory

Wiemels Lab USC and de Smith lab USC

Childhood Cancer Research Topics

Clues to Childhood Cancer

On this page we describe some of the longstanding efforts into discovering causes of childhood cancers, observations over the years and recent findings on these topics, and how this data may help us prevent childhood cancer.

GENETICS AND PEDIATRIC LEUKEMIA

Germline genetic variation is known to contribute to an individual’s risk of developing diseases such as cancer. Common genetic risk variants have been identified through genome-wide association studies (GWAS) that scan the genome for basepair changes in DNA which occur at significantly different frequencies in cases than in controls.

There have been several GWAS of childhood acute lymphoblastic leukemia (ALL) to date, which have discovered at least 15 genetic risk variants in different genes.

Our group has discovered several of these risk variants in multi-ancestry GWAS of ALL, including cases and controls from our California-based studies.

We have a particular interest in the increased risk of ALL in children of Hispanic/Latino ethnicity, who have the highest incidence of ALL in the United States. GWAS of ALL in Hispanics/Latinos in California, as well as including large numbers of Hispanic/Latino ALL cases and controls in our multi-ancestry genetic studies, have helped us to identify novel genetic risk genes and to pinpoint the likely causal variants at several childhood ALL risk loci.

In ongoing research, we are combining existing and new GWAS data to perform comprehensive genetic analyses of ALL in Hispanics/Latinos, including GWAS, admixture mapping, and polygenic risk score analysis, to try to understand the genetic contribution to this disparity in disease incidence.

We are also involved in a global collaborative study through the Childhood Leukemia International Consortium (CLIC) to perform the largest multi-ancestry GWAS of ALL to date. In addition, we have developed a California-based study of familial cancers to investigate the contribution of less common, or rare, germline variants with stronger impacts on childhood leukemia risk.

Our ultimate goal is to have a full understanding of the genetic contribution to childhood leukemia development, which may enable us to identify children most at risk of disease and to guide precision prevention strategies.

INFECTIONS AND CHILDHOOD LEUKEMIA

A rich and consistent set of research has shown that patterns of infection influence childhood acute lymphoblastic leukemia (ALL) risk. For instance: being a first born child carries a higher risk of ALL as the younger children are exposed to more infections brought home by the older children.

Also, a normal course of vaccinations provides decreased risk of leukemia (compared to unvaccinated children), showing that immune “exercise” decreases risk.

Read more about Infections and childhood leukemia…

ETIOLOGY OF ACUTE PROMYELOCYTIC LEUKEMIA

Childhood leukemia is a disease of many different subtypes. We study one of them named “acute promyelocytic leukemia” (APL) that has unique features:

(i) the disease is more common in Latino countries than other parts of the world, and

(ii) the disease occurs sometimes as secondary cancer (after prior chemotherapy), suggesting a chemical cause.

Read more about acute promyelocytic leukemia in children…

INCREASED LEUKEMIA RISK IN CHILDREN WITH DOWN SYNDROME

One of the earliest identified risk factors for childhood leukemia was Down syndrome (DS).

Children with DS, who are born with an extra copy of chromosome 21 (i.e. trisomy 21), have ~20-fold increased risk of developing B-cell acute lymphoblastic leukemia (B-ALL) and ~500-fold risk of acute megakaryoblastic leukemia (AMKL, which is usually very rare in the general population).

Experimental studies have shown that trisomy 21 affects the normal development of blood cells.

Read more about Down Syndrome and leukemia…

IS THERE A SPECIFIC VIRUS?

Patterns of infections and antigenic exposures were long theorized to contribute to the development of childhood leukemia presumably through dysregulation of the immune system at an early age. Recent evidence implicates cytomegalovirus (CMV) as a specific infectious risk factor in the development of childhood ALL. This is the first time a specific infectious agent was implicated.

CMV is part of the Herpesviridae family, and is a common infection in the general population, infecting 30-60% of pre-pubescent children and up to 90% of the population by the age of 50 years.

Primary CMV infection can go unnoticed with mild clinical symptoms; however, even immune competent hosts cannot eradicate the virus, and CMV establishes lifelong latent infection within the host. CMV distorts host innate and adaptive immunity by interfering with cytokine activity, natural killer cell function, T cell response, chemokine activity, and inhibiting apoptosis.

CMV also can dysregulate the immune response to subsequent antigenic exposures. Though CMV is not proven to be an oncogenic virus directly contributing to hematopoietic malignancies, it has been shown to promote tumor growth in other malignancies, most notably glioblastoma multiforme, and exhibits characteristics that overlap with many of the hallmarks of cancer.

In our prior work, we found that children newly diagnosed ALL cases were more likely to have detectable CMV DNA in the bone marrow at diagnosis compared to AML patients who are equally as immunocompromised. In two separate cohorts we showed that children with CMV exposure in utero or early childhood are more likelihood to develop ALL in childhood.

We also found CMV to be associated with certain subtypes of ALL, specifically B-ALL and the high hyperdiploid subtype, that an inflammatory gene expression signature is associated with CMV-positive lymphoblasts, and an association between ALL predisposition genes and CMV-status at ALL diagnosis. The immune dysregulatory properties of CMV in combination with the growing body of evidence associating CMV with ALL lead us to the hypothesis that CMV exposure in utero or early childhood results in immune dysregulation in response to subsequent childhood infections allowing for the expansion of pre-leukemic clones and ultimately leading to overt leukemia.

CMV also provides for us a potential target for therapy, which we will explore in the future.

PARENTAL SMOKING AND CHILDHOOD LEUKEMIA

All body cells carry the same DNA – but each cell has a distinct purpose. How does a blood cell differ from a muscle cell or brain cell? The answer lies in the “epigenome” which is essentially the “operating system” of the genome, running a different program in each cell type. These programs are under tight regulation and are set down early in tissue development.

The most primal epigenetic characteristic is DNA methylation placed upon “C” residues on the DNA stand both at specific sites and across multiple genes and genomic regions.

Here, we study these DNA methylation patterns. Cancer is a product of both genetic and epigenetic changes that promote uncontrolled growth of a tissue. In this project we study both the DNA methylation changes that differentiate childhood ALL cells from normal precursor blood cells – while also identifying those epigenetic changes that have already altered from the normal at the time of the birth of the child.

Most DNA methylation patterns are laid down in the first days and weeks of gestation – the most vulnerable time for aberrations to occur. Environmental factors, such as parental smoking, nutrition, pesticides and air pollution, all may impact DNA methylation at this vulnerable time, establishing cells with altered DNA methylation impacting leukemia risk (without causing DNA mutations).

We try to link up these early changes with DNA methylation patterns in the leukemia cells with this “meet in the middle” approach – further delineating the mechanisms by which environmental factors may induce risk to childhood ALL.

ETIOLOGY OF BRAIN CANCERS IN CHILDREN

Children can get brain tumors and for the most part, we still don’t understand why. For adults, mutations took decades to accumulate, and when key genes (oncogenes or tumor suppress genes) are affected, the chance of getting brain tumor increases. However, in children, there is not much time for detrimental mutations to accumulate, they could still develop a variety of brain tumors, some of them very aggressive.

Here we investigate why children develop brain tumors, for example gliomas. By combining a variety of data including DNA sequences, key chemical modifications of DNA, and exposures to chemicals from the surrounding environment, we aim to identify risk factors of brain tumors and their disease inducing pathways.

For example, we recently discovered that a variant in the mitochondria is associated the risk of childhood glioblastoma, one of the most malignant brain tumors with very poor prognosis. This variant was previously reported to affect height and hearing, but was never tied to cancer risk. This gave us new insights into how energy pathways could play a role in glioblastoma initiation.

Work is ongoing in our lab to deepen the understanding of etiology of childhood brain tumor, and how we can better predict its risk.

Recent Advances in Pediatric Cancer Research

Affiliations.

• 1 Pediatric Oncology Branch, NCI, Bethesda, Maryland. [email protected].
• 2 Osteosarcoma Institute, Dallas, Texas.
• 3 Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, California.
• PMID: 34561271
• PMCID: PMC9725930
• DOI: 10.1158/0008-5472.CAN-21-1191

Over the past few years, the field of pediatric cancer has experienced a shift in momentum, and this has led to new and exciting findings that have relevance beyond pediatric malignancies. Here we present the current status of key aspects of pediatric cancer research. We have focused on genetic and epigenetic drivers of disease, cellular origins of different pediatric cancers, disease models, the tumor microenvironment, and cellular immunotherapies.

©2021 American Association for Cancer Research.

Publication types

• Research Support, N.I.H., Intramural
• Biomedical Research / methods*
• Epigenomics*
• Genomics / methods*
• Immunotherapy*
• Neoplasms / diagnosis*
• Neoplasms / genetics
• Neoplasms / therapy*

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• Z99 CA999999/ImNIH/Intramural NIH HHS/United States

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• Volume 13, Issue 12
• Research priorities for children’s cancer: a James Lind Alliance Priority Setting Partnership in the UK
• Article Text
• Article info
• Citation Tools
• Rapid Responses
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• http://orcid.org/0000-0002-6015-6993 Susie Aldiss 1 ,
• Rachel Hollis 2 ,
• Bob Phillips 3 , 4 ,
• http://orcid.org/0000-0002-0708-0918 Ashley Ball-Gamble 5 ,
• Alex Brownsdon 6 ,
• Julia Chisholm 7 , 8 ,
• Scott Crowther 9 ,
• Rachel Dommett 10 ,
• Jonathan Gower 11 ,
• http://orcid.org/0000-0001-8570-9374 Nigel J Hall 12 , 13 ,
• Helen Hartley 14 ,
• Jenni Hatton 15 ,
• Louise Henry 7 ,
• Loveday Langton 16 ,
• Kirsty Maddock 2 ,
• Sonia Malik 17 ,
• Keeley McEvoy 18 ,
• http://orcid.org/0000-0001-8087-8638 Jessica Elizabeth Morgan 3 , 19 ,
• Helen Morris 20 ,
• Simon Parke 21 ,
• Sue Picton 2 ,
• Rosa Reed-Berendt 22 ,
• Dan Saunders 23 ,
• Andy Stewart 24 ,
• Wendy Tarplee-Morris 25 ,
• Amy Walsh 26 ,
• Anna Watkins 16 ,
• David Weller 27 ,
• http://orcid.org/0000-0002-8125-4584 Faith Gibson 1 , 28
• 1 School of Health Sciences , University of Surrey , Guildford , UK
• 2 Leeds Children's Hospital , Leeds , UK
• 3 Department of Paediatric Haematology and Oncology , Leeds Teaching Hospitals NHS Trust , Leeds , UK
• 4 Hull-York Medical School and Centre for Reviews and Dissemination , University of York , York , UK
• 5 Children’s Cancer and Leukaemia Group , Leicester , UK
• 6 Patient Representative on the Children’s Cancer Priority Setting Partnership Steering Group , London , UK
• 7 The Royal Marsden NHS Foundation Trust , Sutton , UK
• 8 Institute of Cancer Research Sutton , Sutton , UK
• 9 Parent Representative on the Children’s Cancer Priority Setting Partnership Steering Group , Coventry , UK
• 10 Bristol Royal Hospital for Children , Bristol , UK
• 11 James Lind Alliance , National Institute for Health Research Evaluation, Trials and Studies Coordinating Centre , Southampton , UK
• 12 Southampton Children's Hospital , Southampton , UK
• 13 University of Southampton Faculty of Medicine , Southampton , UK
• 14 Alder Hey Children's NHS Foundation Trust , Liverpool , UK
• 15 University Hospitals Birmingham NHS Foundation Trust , Birmingham , UK
• 16 Parent Representative on the Children’s Cancer Priority Setting Partnership Steering Group , London , UK
• 17 Young Lives Vs Cancer , London , UK
• 18 Medical Needs Teaching Service , Leeds Children's Hospital , Leeds , UK
• 19 Centre for Reviews and Dissemination , University of York , York , UK
• 20 Children, Teenage and Young Adult Cancer Operational Delivery Network, South West , Bristol , UK
• 21 Royal Devon and Exeter NHS Foundation Trust , Exeter , UK
• 22 Psychological Services , Great Ormond Street Hospital for Children NHS Foundation Trust , London , UK
• 23 The Christie NHS Foundation Trust , Manchester , UK
• 24 Parent Representative on the Children’s Cancer Priority Setting Partnership Steering Group , Perth , UK
• 25 The Little Princess Trust , Hereford , UK
• 26 Parent Representative on the Children’s Cancer Priority Setting Partnership Steering Group , Keswick , UK
• 27 The University of Edinburgh, Edinburgh Medical School , Edinburgh , UK
• 28 Centre for Outcomes and Experience Research in Child Health, Illness and Disability (ORCHID) , Great Ormond Street Hospital For Children NHS Foundation Trust , London , UK
• Correspondence to Susie Aldiss; s.aldiss{at}surrey.ac.uk

Objectives To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda.

Design James Lind Alliance Priority Setting Partnership.

Setting UK health service and community.

Methods A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities.

Participants Children and survivors of childhood cancer, diagnosed before age 16, their families, friends and professionals who work with this population.

Results Four hundred and eighty-eight people submitted 1299 potential questions. These were refined into 108 unique questions; 4 were already answered and 3 were under active study, therefore, removed. Three hundred and twenty-seven respondents completed the shortlisting survey. Seventy-one children submitted questions in the children’s surveys, eight children attended a workshop to prioritise these questions. The Top 5 questions from children were taken to the final workshop where 23 questions in total were discussed by 25 participants (young adults, carers and professionals). The top priority was ‘can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?’

Conclusions We have identified research priorities for children’s cancer from the perspectives of children, survivors, their families and the professionals who care for them. Questions reflect the breadth of the cancer experience, including diagnosis, relapse, hospital experience, support during/after treatment and the long-term impact of cancer. These should inform funding of future research as they are the questions that matter most to the people who could benefit from research.

• paediatric oncology
• patient participation
• surveys and questionnaires

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information. Further data regarding the original submissions to the surveys are available from: https://www.jla.nihr.ac.uk/priority-setting-partnerships/childrens-cancer/ .

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/ .

https://doi.org/10.1136/bmjopen-2023-077387

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STRENGTHS AND LIMITATIONS OF THIS STUDY

We made use of the well-established and transparent James Lind Alliance methodology and clearly describe the process and decision-making which led to the final Top 10 research priorities.

The process followed ensures that these priorities came directly from those who are the most affected by childhood cancer but rarely influence the research agenda.

We ensured the priorities of patients/survivors, parents/relatives/friends and professionals were given equal weighting at the interim priority setting stage.

We used innovative methods to hear directly from children about their priorities for future research through surveys and a workshop specifically designed for them.

Under-represented groups in the survey submissions included people from minority ethnic groups, males and primary healthcare professionals.

Introduction

Annually, there are around 1800 new cases of cancer in children in the UK. 1 While research over the last four decades has dramatically increased the overall 5-year survival rate for all childhood cancers to around 84%, 2 further research is needed to not only improve outcomes for all types of cancer, but to support all children to live long, healthy and happy lives.

Historically, topics of healthcare research in children’s cancer have been driven by perspectives of researchers and the pharmaceutical industry, meaning what is most important to children, survivors, their families and the professionals who care for them, has sometimes been overlooked. Prioritising areas for research as identified by children and carers is crucial. There is increasing evidence that research questions and outcomes prioritised by professionals may not be aligned to those experiencing the disease. 3 Patients and carers tend to prioritise non-drug treatment research while ongoing research strategies are dominated by drug evaluations. 4 This mismatch in priorities is particularly relevant for children due to their unique physiological and psychosocial status and relative rarity of cancer. Increasingly, research funders are asking if proposed research is a priority for patients.

The James Lind Alliance (JLA) is a non-profit-making initiative bringing together patients, carers and professionals in Priority Setting Partnerships (PSPs) focusing on specific health conditions http://www.jla.nihr.ac.uk/priority-setting-partnerships / ). JLA PSPs identify and prioritise unanswered questions, so researchers and research funders are aware of the issues that matter most to those who could benefit from that research. 5

In 2019, Children’s Cancer and Leukaemia Group ( https://www.cclg.org.uk/ ) and The Little Princess Trust ( https://www.littleprincesses.org.uk/ ) partnered with the JLA on the Children’s Cancer PSP. One of our primary goals was to prioritise the voice of children about what research should be undertaken. Previous PSPs have sought to involve children and young people, but in the final reporting it is evident that few children, especially young children, had been engaged through the process. 6 We recognised the challenges of engaging with these populations, in terms of reach and accessibility of information and determined we would invest time and resources, in exploring and resolving any challenges that could impact on participation.

Following the JLA methodology, we aimed to conduct a UK-wide research prioritisation exercise for childhood cancer to inform decisions of research funders and support the case for research in this underserved group. 7

Methodology followed the JLA process, 5 the protocol is available from: https://www.jla.nihr.ac.uk/priority-setting-partnerships/childrens-cancer/ .

Project management

There was a coordinating team of four researchers, nurses and clinicians. An expert steering group (all coauthors) oversaw the project, approved aims/objectives, survey materials, contributed to data analysis and summary question formation, and provided expert opinions for evidence checking. The steering group included parents of a child with cancer (n=5); an adult survivor of childhood cancer; a range of professionals reflecting the multidisciplinary nature of the care of children with cancer including: a teacher, general practitioner, surgeon, pharmacist, dietitian, speech and language therapist, clinical psychologist, physiotherapist, nurses (n=2), doctors (n=6) and representatives from the third sector (n=3), including the charities funding the project. The JLA chair (JG) provided neutral facilitation of meetings. The steering group identified potential partners, mainly children’s cancer charities and professional networks, who were approached to assist with survey dissemination.

This project focused on cancer and cancer-like conditions in children aged 0 to <16 at initial diagnosis. The scope, kept intentionally broad, included questions on any aspect of the cancer experience ( figure 1 ).

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Pathway of care included in the project scope.

Our aim was ‘to identify gaps and unanswered questions in research about children’s cancer from patients, carers and professionals’ perspectives and then prioritise those that these groups agree are the most important for research to address.’

Figure 2 summarises the complete process.

Overview of the Children’s Cancer Priority Setting Partnership methodology and results.

Stage 1a: gathering questions: initial survey

The survey was developed by the steering group and built using Qualtrics software. It was piloted with eight adult survivors of childhood cancer, nine parents and two professionals outside the steering group and adapted to incorporate their feedback. The survey launched on 9 September 2020 and closed on 8 January 2021. The following groups were invited to participate:

People diagnosed with cancer before their 16th birthday.

Relatives/friends/partners/carers of someone diagnosed with cancer before their 16th birthday.

Professionals involved in diagnosing or treating children who have cancer or had cancer under 16.

Professionals involved in the care of children who have cancer or had cancer under 16 and/or their families.

Respondents could submit up to eight questions about any aspect of children’s cancer they considered important and unanswered. Basic demographic data were requested, and a box was available for free-text comments. Partners promoted the survey through websites, social media, newsletters and email.

Stage 1b: gathering questions from children and young people

A subgroup of the steering group was established to focus on our engagement with children. This consisted of two researchers, a teacher, doctor, health play specialist, parent, clinical psychologist and charity representative. Our initial intention had been to run a series of face-to-face workshops with children to collect questions, this was not possible due to the COVID-19 pandemic until the final workshop in the PSP process.

We determined that the best way to reach children would be through their parents/carers. Three survey versions were built using Qualtrics software, aimed at children of different ages (4–7, 8–12, 13–15 years). Surveys were piloted with three children and young people. They varied in complexity of language used in the introduction and questions, and surveys for young people contained more questions seeking demographic information: participants could complete whichever survey version they preferred. Animations were developed to assist parents explain the project and survey to their child(ren) (surveys/animations available here: https://www.jla.nihr.ac.uk/priority-setting-partnerships/childrens-cancer/ ).

Surveys were launched on 6 September 2021 and closed on 16 November 2021 inviting participants who:

Were diagnosed with cancer before their 16th birthday.

Have a brother or sister with cancer now or who had cancer when they were younger (diagnosed before their 16th birthday).

Have a friend with cancer now or who had cancer when they were younger (diagnosed before their 16th birthday).

Respondents were invited to submit up to eight questions/topics about any aspect of children’s cancer they considered important. Surveys were promoted through the PSP’s Partners, social media and posters were sent to all UK Principal Treatment Centres.

Stage 2a: refining questions from the initial survey

Submitted questions were examined in detail and free-text sections studied for further questions.

Organising the questions

Initial coding was carried out by coordinating team members (SA and FG). Questions were grouped into themes. During coding, potential ‘out-of-scope’ questions were identified (see box 1 for criteria used). Identification of out-of-scope questions was an iterative process, checked and agreed by the steering group.

Out-of-scope question categories and examples

The question was ambiguous, was interpreted in different ways by steering group members and the meaning could not be resolved following discussion:

‘Remaining scar tissue’

‘How research is going’

Questions not answerable by research:

‘Why does paediatric cancer research receive so very little funding?’

‘Who is present when you give the diagnosis’.

Questions submitted by people whose experience was not of childhood cancer as defined by our project scope—there were a few parent respondents whose child was over 16 at diagnosis. These questions were checked to verify that all the themes within them had been covered by ‘in scope’ questions.

Similar questions were grouped to form summary questions. The aim was to retain the sense of what respondents meant, but in the form of a clear question. Steering group members met online in small groups to review summary questions within their area of expertise/experience, to confirm the grouping of questions, and wording of each summary question. The steering group reviewed the whole summary question list.

Evidence searching

Searches were undertaken to identify questions answered by existing evidence. A search strategy was agreed with the steering group (see question verification form: https://www.jla.nihr.ac.uk/priority-setting-partnerships/childrens-cancer/ ). Searches were carried out by SA in January–May 2022. Searches were limited to evidence published in the last 5 years (since January 2017) and focused on evidence gathered from multiple studies (eg, systematic reviews, qualitative meta-synthesis). Searches were undertaken for ongoing studies which included personal communication with experts in the field and steering group members’ knowledge of current research.

Stage 2b: refining questions from children and young people

The same process was followed for refining questions from the children and young people’s surveys. Questions were grouped into themes by SA with support from FG, similar questions were merged, and summary questions created. Out-of-scope questions were removed, if they were unrelated to cancer or were unclear (eg, ‘cost to hospital’, ‘wildlife’). The subgroup met online to review summary questions and out-of-scope questions, with further checking undertaken via email until agreement was reached.

Stage 3: question prioritisation

Shortlisting survey preparation.

The steering group discussed whether to take all unanswered questions to the shortlisting survey or shorten the list to make the survey quicker to complete. The group chose not to remove any questions.

To ensure questions were easy to understand, they were reviewed by patient and parent members of the steering group and a health information specialist from one of the funding charities. Questions were simplified following this review and definitions of words added.

Shortlisting survey

The shortlisting survey was created using Qualtrics software, launched 3 August 2022 and closed 30 September 2022. Invitations mirrored the initial survey, and it was publicised using the same methods. Initial survey participants who left contact details were emailed directly.

To shorten the question list, respondents were invited to read the 101 questions and select those that were most important to them. Questions selected were added to their own personal ‘shortlist’ ready for them to make their final selection of up to 15 questions. Survey fatigue was minimised by randomisation of section order and questions. This randomisation aimed to limit question selection bias, for example, always selecting the first or last presented questions.

Questions were grouped into:

Side effects and management.

Physical activity, play and therapies.

Long-term effects and follow-up care.

Communication and information sharing.

Psychological and social well-being.

Food and nutrition.

Healthcare delivery.

Causes of cancer, diagnosis and research.

Results were analysed in three groups: (1) patients/survivors, (2) parents/friends/relatives and (3) professionals. This gave equal weight to each group’s choices as more parents/friends/relatives took part. Questions were given a rank depending on the number of votes and ordered from highest to lowest for each group. The steering group reviewed and compared respondent groups and decided to take the Top 10 questions for each of the three groups to the workshop. This ensured that what was important to each group would be considered and resulted in 21 questions being shortlisted, as some questions were shared priorities.

Stage 4a: workshop with children and young people

The children and young people’s workshop took place in October 2022. The workshop was facilitated by SA and FG following the methodology used by the Juvenile Idiopathic Arthritis PSP. 8 Children were given a choice of seven envelopes, each containing questions on a different topic with a total of 31 questions. Topics were as follows:

Family, friends and pets.

Treatments and medicines.

Being poorly, side effects and long-term effects.

Being in hospital.

Emotions, worries and getting help or support.

School and education.

Getting the information you need.

Each participant chose the topic which was most important to them. Envelopes were opened, and participants placed the questions on the table in groups of most, medium or least important. Participants were invited to add more questions if anything of importance to them was missing. They were given three stickers to vote for their top three questions. Questions were placed in order of most to least votes and a discussion followed to agree the ‘Top 5’; these were taken to the final workshop.

Stage 4b: Top 10 prioritisation

The final prioritisation workshop took place in November 2022. Participants who left their contact details in the survey were invited to attend as were patient and parent representatives on the steering group. Steering group contacts were used to ensure participation from a broad range of professionals across the field.

Prior to the workshop, participants were asked to individually rank the questions in order of importance. The workshop was chaired by JG and supported by two JLA facilitators. Participants were split into three preallocated groups ensuring a balance of multidisciplinary professionals, young adults and parents/relatives. In each group, participants shared their three highest and lowest ranking questions. Participants were told which questions were in the children’s Top 5.

During facilitated discussion, the groups ordered the questions from highest to lowest priority. The ranking from the three groups were combined. In a second session, groups were reallocated and the combined ranking was discussed. Following this discussion, the group rankings were again collated, and all participants formed one group to debate and agree the Top 10.

Patient and public involvement

Parent and patient representatives were involved as equal members of the steering group and in all stages of the prioritisation process. Patients and carers were survey respondents. Children were included in a parallel process. Young adults and parents/relatives attended the final prioritisation workshop alongside professionals as equal stakeholders. Participants were reimbursed for travel/overnight accommodation costs.

Figure 2 provides an overview of the number of respondents at each stage.

Initial survey

Four-hundred and eighty-eight people submitted 1299 questions. Respondents included 49 (10%) patients/survivors, 291 (60%) parents/relatives/friends and 148 (30%) professionals. Most parents/relative/friends were parents (n=271; 93%), 15 (5%) were relatives and 5 (2%) friends. Online supplemental material 1 shows respondent demographics.

Supplemental material

One-hundred and thirty-nine out-of-scope questions were removed; box 1 illustrates examples. Following the combining of similar questions and rewording to form summary questions, 108 questions remained.

Analysis of uncertainties

Four questions were already answered, and three the focus of ongoing studies. For some questions, no reviews or ongoing studies were identified. If reviews only partly answered a question, these were recorded as unanswered. The steering group discussed all questions ensuring consensus agreement of answered/unanswered questions; 101 questions were unanswered.

Children and young people’s surveys

Seventy-one respondents submitted 252 questions/topics. Sixty-one respondents were children and young people who had experienced cancer (aged 3–21) and 10 were siblings (aged 4–19). No friends participated. See online supplemental material 2 for demographics. For brevity, we refer to submissions as ‘questions’; nearly all submissions were not written as questions. Thirteen questions were identified as out-of-scope and removed. Responses were summarised into 24 questions.

Ratings were submitted by 327 respondents. Like the initial survey, the largest respondent group was parents/relatives/friends (64%, n=210; including 197 parents, 10 relatives, three friends), followed by professionals (28%, n=90) and patients/survivors (8%, n=27). See online supplemental material 3 for demographics.

Children and young people’s workshop

Eight children and young people aged 8–16 attended; three were siblings. Their diagnoses included lymphoma and leukaemia.

During discussion, seven additional questions were created about family, friends and pets and six were added on topics that were important to participants. The Top 5 are shown in table 1 . Three of the questions were closely aligned to those already going to the final workshop from the shortlisting survey (priorities 2, 4 and 5). For priority 4, the children and young people’s version of the question had an extra part about starting treatment in the right place, this version was taken to the final workshop. Priorities 1 and 3 from children and young people were new and were added into the list, making 23 questions in total for the final workshop.

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Children and young people’s Top 5 and questions for the final workshop

Final workshop

Twenty-five participants attended: 4 young adults who had experienced childhood cancer, 5 parents and 1 grandparent of a child who had cancer, and 15 professionals who work with this population. Professional roles varied and included nurses, doctors, a social worker, health play specialist, dietitian, clinical psychologist, physiotherapist and chaplain. One participant was a steering group member.

Top 10 prioritisation strategies

Although the three groups worked independently, they all applied similar prioritisation strategies:

Ensuring children’s views were represented

All groups wanted to ensure the Top 10 questions included most, if not all, questions from the children’s Top 5. When the groups were told which questions were important to children, those question cards were picked out and moved up the ranking. Most of these questions remained in the Top 10, or just outside, for the duration of the discussions.

Opting for questions that could include other questions/overlap

Groups considered which questions overlapped and could cover other questions. For example, ‘can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?’ mentions side effects and so could include, ‘what are the best ways to reduce, predict and manage the side effects of treatment for children (including life-threatening side effects)?

Opting for questions focused on intervention rather than description

Groups were clear that although it is useful to describe a problem, it is action through intervention that is required to improve children’s and families’ experiences. Therefore, ‘are the psychological, practical and financial support needs of children with cancer, survivors and their families being met during treatment and beyond? How can access to this support be improved and what further support would they like?’ was placed higher in the rankings than ‘what is the psychological and social impact of cancer and treatment on children and their families during treatment and in the long term; what factors affect these impacts?’ as the latter question involves description, rather than action.

Opting for questions that could have wider impact

Initially, most participants selected their top three questions reflective of their personal experience or area they worked within. During discussions, their opinions changed, and groups decided that the Top 10 questions should be generic and have the potential to have the greatest impact on as many children and families as possible. For example, ‘how can experiences of having a Hickman line be improved for children with cancer?’ was considered too specific and did not apply to all children.

Ensuring all themes within the questions were represented

Groups tried to cluster questions into similar themes, such as support, treatment, care, side effects, their aim being to include each ‘theme’ in the Top 10. For example, the question about relapse was moved up during discussions as this was not covered by any other question.

Group discussion and decision-making

From the outset, there were some questions that were high priority for many and stayed high in the Top 10 throughout the workshop. The question ranked as top priority, ‘can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?’ was the top priority for all three groups after the first group discussion. After the second group discussion, all three groups had the same questions ranked one to five, which remained in the same positions in the final Top 10.

The final group discussion focused on whether to include, ‘what is the relationship between chronic fatigue syndrome, fibromyalgia, chronic pain and treatment for childhood cancer?’ in the Top 10 (it was at number 11). This push for inclusion came from two young adults who said these long-term effects had a huge impact on their lives and had experienced a lack of recognition and support. There was a group vote and the decision was made to move this question up to number 10 and move, ‘what are the best ways to provide emotional support for children and their families (1) around the time of diagnosis, (2) during treatment and (3) after treatment (including survivors who are now adults)?’ down to number 11 as this was covered by the broader question, about support at number 3.

The final Top 10 priorities are shown in box 2 alongside the other 13 questions discussed.

Top 10 research priorities for children’s cancer and the additional 13 questions discussed at the workshop

Can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?

Why do children develop cancer (including the role that genetics plays) and could it be prevented?*

Are the psychological, practical and financial support needs of children with cancer, survivors and their families being met during treatment and beyond? How can access to this support be improved and what further support would they like?†

How can we speed up the process of getting diagnosed and starting treatment in the right place?*

Why do children relapse, how can it be prevented and what are the best ways to identify relapse earlier?

How can we make being in hospital a better experience for children and young people? (like having better food, internet, toys and open visiting so other family members can be more involved in the child’s care)*

What are the best ways to ensure children and families get and understand the information they need, in order to make informed decisions, around the time of diagnosis, during treatment, at the end of treatment and after treatment has finished?

What impact does cancer and treatment have on the lives of children and families after treatment, and in the long term; what are the best ways to help them to overcome these impacts to thrive and not just survive?

How can we make more accessible treatments that are closer to home, in shared care hospitals?*

What is the relationship between chronic fatigue syndrome, fibromyalgia, chronic pain and treatment for childhood cancer? (Fibromyalgia is a long-term condition that causes pain all over the body.)

What are the best ways to provide emotional support for children and their families (1) around the time of diagnosis, (2) during treatment and (3) after treatment (including survivors who are now adults)?*

What are the best ways to reduce, predict and manage the side effects of treatment for children (including life-threatening side effects)?

How can transition (moving) from child into adult services be improved for young people who had cancer as a child?

What is the psychological and social impact of cancer and treatment on children and their families during treatment and in the long term; what factors affect these impacts?

How common are the different long-term effects of childhood cancer treatment, how do they change across the lifespan, can we predict them and how can they best be prevented, detected and/or treated?

What are the best ways to support the emotional well-being of professionals who care for children with cancer and their families?

During and after treatment, what issues prevent or encourage physical activity, which interventions are most effective and what should be measured to assess effectiveness?

What are the best ways of making sure people who had cancer as a child receive the information they need about the long-term effects of cancer and treatment?

What fertility preservation options work best for children and teenagers with cancer?

What are the long-term effects of additional medications children with cancer may receive (such as antibiotics, pain killers, laxatives) and how can these effects be reduced?

What are children’s and survivors’ experiences of the side effects and long-term effects of cancer treatment?

How can experiences of having a Hickman line be improved for children with cancer? (A Hickman line is a small tube which is inserted into a vein so that treatments can be given, and blood taken without the repeated need to access veins with a needle. The Hickman line can stay in place for several months.)

What are the best ways to support children as they get older, and their needs change, to understand and take responsibility for their health, and to live with the long-term effects of cancer and treatment?

*These questions were in the Top 5 research priorities identified by children and young people.

†This question was originally not mapped onto the question about emotional support from children and young people, but the workshop participants decided that this question was related as it includes emotional support as well as other types of support.

The Children’s Cancer PSP brought together children, survivors, families and professionals to prioritise research questions on childhood cancer. The Top 10 priorities provide a resource to inform research funding decisions in government and charitable organisations. The top priority is ‘can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?’ This question was ranked as top in the shortlisting survey by all three respondent groups (patients/survivors, parents/relatives/friends and professionals) and placed at number 1 from the start of the workshop by all three discussion groups. This reflects shared priorities of continuing to improve cure rates while minimising treatment toxicity. The Top 10 priorities reflect the breadth of the cancer experience, including diagnosis, relapse, hospital experience, support during/after treatment and the long-term impact. Priorities highlight the need for research strategies to be holistic in their approach rather than solely driven by biological and drug intervention research. It is now critical that funders and researchers ensure future research focuses on what is important to children, survivors, families and professionals. 9

A number of cancer-related PSPs exist, including one in Canada also focusing on childhood cancer ( https://www.jla.nihr.ac.uk/priority-setting-partnerships/pediatric-cancer/top-10-priorities.htm ). The top priority for the Canadian PSP is preventing and managing treatment-related long-term effects which links to the top priority of our PSP and finding ‘kinder’ treatments. Both Top 10 lists feature similar questions on relapse, prevention/detection and questions about psychosocial impact and support. There is an increasing drive to focus on both physical and psychological health during and after cancer. It is already recognised that a cancer diagnosis has serious implications for children and young people’s mental health during and after treatment, 10 11 but this has yet to be systematically investigated, and how best to provide support remains unknown. Psychological support was the top priority in the Teenage and Young Adult Cancer PSP. 12

Challenges, strengths and limitations

The anticipated timeline for this project was two years, it took three. This delay was partly due to the COVID-19 pandemic. The project was resource intensive, requiring input from all steering group members. The challenge of involving professionals with full schedules, and parent/patient representatives with many concerns and commitments, was amplified by the pandemic and our progress reflected this.

The scope of the PSP was intentionally broad to reflect the heterogeneity of childhood cancer, and variation in treatment and experience. This generated a significant workload when sorting and summarising diverse questions, and subsequent literature searching to verify uncertainties.

Engaging with children extended the project timescale; this work had to be carefully planned to ensure our methods were accessible and appropriate. Plans for face-to-face work were revised due to pandemic restrictions. Few priority setting exercises have involved many children and young people. 6 13 Previous PSPs have reflected that they were unable to engage with children as they wished, due to lack of time and resources. 14 It was of utmost importance to our steering group that children’s voices were heard. We consider this aspect of our PSP a success: time and resources invested in engaging with children were worthwhile. Overall, questions from children reflected similar themes as those from adult participants, but there were some additional elements that featured as higher priority for children, such as having treatments closer to home and improving the hospital experience. In the final workshop, participants wanted children’s voices to be heard, resulting in all five of the top priorities identified by children being reflected in the Top 10.

The use of the rigorous and transparent JLA methodology enhances the validity of the process and results. The response from parents/carers to both surveys was high and parent and patient representatives were involved in shaping the project from the outset, as members of the steering group. Their input was key, for example, they helped to ensure the surveys were presented in a user-friendly format and appropriate routes to dissemination were used. Parent/patient representatives reported a positive experience of being involved in the steering group , ‘I wanted to be involved with the PSP because of the exciting opportunity to contribute towards future research topics in childhood cancer, bringing the voice of childhood cancer survivors from a service user perspective and advocating for the cohort. I have found the experience to be extremely positive and engaging. I feel that my presence is valued, and my contributions have been acknowledged and implemented throughout the process.’

Absent voices must be considered as a limitation. Of note, the majority of respondents described themselves as White. The priorities, therefore, represent the views of the majority, White population, which has been observed in other PSPs. 15 Males were also under-represented. We did not ask in the surveys whether respondents have a disability (whether resulting from treatment or not) and so cannot comment on what impact this might have had on prioritisation.

Primary care has an important role in the care of children with cancer from diagnosis into survivorship. 16 There was a primary care representative on the steering group and at the final workshop, but none responded to the initial survey, and only one to the shortlisting survey. The voices of these professionals are absent from the questions collected.

Implications and dissemination

The Top 10 have been circulated on social media and via supporter newsletters/websites by the PSP funding charities and our Partners. Dissemination includes publication of a final report with an associated launch event, peer-reviewed publications and conference presentations. We will report the details of our engagement with children in a separate publication and are working with the JLA to develop guidance for future PSPs.

Our aspiration is that these prioritised questions will help to direct and shape future research. The uncertainties identified are the outcome of a systematic and transparent process and provide funders with clear guidance on the highest priorities for future research, voted on by end-users of research. Identifying clear areas for future research allows research funders to target funds effectively and inform fundraising activities. We plan to hold a meeting with funders to promote the priorities and encourage funding calls focused on the priority areas.

When selecting questions to be included in the Top 10, workshop participants intentionally opted for broad questions, to capture the widest range of issues. This is common in JLA PSPs, the questions, therefore, reflect broad topic areas for research; further refinement is required to transform topics into answerable research questions. 17 This PSP also demonstrates that where sufficient expertise and resources are available, involvement of young children can be achieved. Therefore, funding guidance should encourage applicants to undertake such work.

Some questions submitted were outside the scope of the PSP and were removed. Many suggested a knowledge gap. The steering group considered these questions to be important and is determined to ensure these submissions are not ‘lost’. We will look at how these questions, statements and service enquiries can be best used to improve information signposting. Questions were submitted regarding disparity in funding between childhood and ‘adult’ cancers. These questions were removed, as they are not amenable to research, but we intend to share them through a commentary piece, as they reflected strong opinions and perceptions that would benefit from further exploration and articulation.

We have identified shared research priorities for children’s cancer using a rigorous, person-centred approach involving stakeholders not typically involved in setting the research agenda, including children. Resulting questions reflect the breadth of the cancer experience for children and families, including diagnosis, relapse, hospital experience, support during and after treatment and the long-term impact of cancer. These must inform funding of future research, with priority questions evidenced by researchers.

Ethics statements

Patient consent for publication.

Not applicable.

Ethics approval

This study involves human participants but ethical approvals are not required for JLA Priority Setting Partnerships as per JLA and National Health Services Patient Safety Agency National Research Ethics Service guidance ( https://www.invo.org.uk/posttypepublication/public-involvement-in-research-and-research-ethics-committee-review/ ). The James Lind Alliance does not define priority setting exercises as a research study.

Acknowledgments

The Children’s Cancer PSP would like to thank everyone who took the time to send in their questions and vote on the importance of them. Thank you also to the children, young people, parents, relatives and professionals who attended the workshops. We would like to thank Angela Stewart for providing administrative support to the PSP. We would also like to thank the previous members of the steering group: Martin English, Penelope Hart-Spencer, Charmaine Jagger and Angela Polanco.

• Cancer Research UK
• Chalmers I ,
• Atkinson P ,
• Fenton M , et al
• Hall M , et al
• James Lind Alliance
• Luchtenberg ML ,
• Verhagen AAE , et al
• Phillips B , et al
• Aussems K ,
• Schoemaker CG ,
• Verwoerd A , et al
• Berkman AM ,
• Robert RS ,
• Roth M , et al
• Sharkey CM ,
• Espeleta HC ,
• Traino KA , et al
• Phillips RS , et al
• Odgers HL ,
• Lopez-Vargas P , et al
• Simkiss D ,
• Busk M , et al
• Biglino G , et al
• Szewczuk MR
• Crocker JC , et al

Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

• Data supplement 1
• Data supplement 2
• Data supplement 3

Twitter @AldissSusie, @ashleysgamble, @nigel_j_hall, @drjessmorgan

Contributors All authors (SA, RH, BP, AB-G, AB, JC, SC, RD, JG, NJH, HH, JH, LH, LL, KiM, SM, KeM, JEM, HM, SPa, SPi, RR-B, DS, AS, WT-M, AWalsh, AWatkins, DW and FG) were part of the Children’s Cancer Priority Setting Partnership steering group or coordinating team and made substantive contributions to the conduct of the study, overseeing all aspects of the work. All authors contributed to protocol design, survey refining, data cleaning and refining questions submitted in the initial survey. The project was managed by SA and FG (guarantor), BP, RH and JG. SA, FG, JEM, SM, LL, KeM and RR-B were part of a subgroup overseeing engagement with children throughout the PSP process. Specific contributions included: survey design (SA), coding the survey submissions (FG and SA), searching and checking uncertainties (SA, BP), managing data entry (SA). All authors reviewed and approved the final version of this paper.

Funding This work was supported by Children’s Cancer and Leukaemia Group (CCLG) and Little Princess Trust. No grant award number available. Dr Julia Chisholm is supported by the Giant Pledge through the Royal Marsden Cancer Charity and this independent research is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. FG is supported in-part by the Great Ormond Street NIHR Biomedical Research Centre.

Competing interests None declared.

Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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Childhood Cancer Facts

We’ve gathered answers to your most frequently asked questions about childhood cancer, including statistics, resources and more.

How common is childhood cancer?

About 1 in 285 children will develop cancer before the age of 20.

How many children are diagnosed with cancer each day?

47 children are diagnosed with cancer every day in the U.S.

How many types of childhood cancer are there?

There are more than 12 major types of childhood cancers and over 100 subtypes.

What is the survival rate for childhood cancer?

1 in 7 children diagnosed with cancer in the U.S. will not survive. Survival rates differ for different types of childhood cancers – but overall, childhood cancer remains the most common cause of death by disease among children in the U.S.

What are the most common types of childhood cancer?

The two most common types of childhood cancers are leukemias and brain/central nervous system cancers. 

Is childhood cancer rare?

Technically, yes. A rare disease is defined as one that affects a population smaller than 200,000 – meaning that all childhood cancers are technically considered rare. But we believe no childhood cancer is too rare to deserve research funding. Read our article: Why childhood cancers are considered “too rare” to get research funding.

How much funding goes to childhood cancer research each year?

It’s hard to pinpoint exactly how much funding goes to childhood cancer research, but it pales in comparison to funds available for research into adult cancers. In fact, as a percentage of cancer research funding from the federal government, childhood cancer research funding is in the single digits. Over half of all funds dedicated to childhood cancer research are from donors like you. In short, without your support, vital childhood cancer research would not move forward.

How does childhood cancer affect families?

Childhood cancer impacts the whole family – in fact, one in four families lose more than 40% of their annual household income as a result of childhood cancer treatment-related work disruption. One in three families face other work disruptions such as having to quit work or change jobs.

Siblings of children with cancer are at risk for emotional and behavioral difficulties, such as anxiety, depression and post-traumatic-stress disorder.

Symptoms of post-traumatic stress disorder are well documented for parents whose children have completed cancer treatment.

Is childhood cancer different from adult cancers?

Yes – the two most common causes of cancer in adults are smoking and obesity. In children, the most common cause of cancer is randomly acquired DNA mutation. In short, childhood cancer is a disease of unfortunate random chance.

For many adult cancers, we know what puts adults at higher risk, and we can prevent many cancers by changing behaviors or treat them effectively by screening and catching them early. For kids, prevention may not be possible – some childhood cancers begin developing before the child is even born.

How can I support a family facing childhood cancer?

If you feel compelled to help a family experiencing cancer, know that your thoughtfulness could be a huge stress relief that’s remembered for a lifetime. Here are 5 ways to support a family facing cancer.

Looking for even more? Check out our blog post: “Is there anything I can do?” There is, and here’s how.

What should I write in a card to a child who has cancer?

You don’t want to write the wrong thing, but you want them to know you care… so where to start? Here are 5 things to write in a card to a child or family dealing with childhood cancer.

Looking to go above and beyond a card? Read our blog: Tips for bringing a meal to a cancer family.

What should I not say to a family facing cancer?

A family that has just received a new cancer diagnosis may be feeling very fragile – meaning even the most well-intentioned questions or comments can sting. Read our blog: What to Say (and What Not to Say) to a Family Facing Cancer where cancer parents share what they’ve found helpful, and what is better left unsaid.

What are the side-effects of childhood cancer treatment?

Side-effects of cancer treatment can range widely, and they are dependent on a child’s specific treatments. But some of the most common side-effects of childhood cancer treatment include:

Acute side-effects:

• Mouth, gum and throat sores
• Weight changes
• Increased risk of infection

What are some late-effects of childhood cancer treatment?

Because kids are still growing and developing during cancer treatment, and these treatments are so harsh, many survivors face late-effects years or even decades after treatment is over. Learn more about childhood cancer survivorship here.

Some common late-effects include:

• Mental health issues and memory loss
• Hearing loss
• More cavities
• Heart and other organ damage
• Increased risk of secondary cancers
• Infertility
• Nerve damage, pain and weakness
• Stunted bone growth

Looking for more? Check out our blog: Seven childhood cancer facts to share this childhood cancer awareness month.

What is Childhood Cancer Awareness Month?

Childhood Cancer Awareness Month is held every September to raise awareness about childhood cancer, its impact on children and families, and the need for improved research, treatment, and support. It aims to educate the public, advocate for increased funding and resources, and foster community engagement to ultimately improve the lives of children diagnosed with cancer.

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Mayo researchers invented a new class of AI to improve cancer research and treatments

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By Colette Gallagher

Mayo Clinic researchers recently invented a new class of artificial intelligence (AI) algorithms called hypothesis-driven AI that are a significant departure from traditional AI models which learn solely from data.

In a review published in  Cancers,  the researchers note that this emerging class of AI offers an innovative way to use massive datasets to help discover the complex causes of diseases such as cancer and improve treatment strategies.

"This fosters a new era in designing targeted and informed AI algorithms to solve scientific questions, better understand diseases, and guide individualized medicine," says senior author and co-inventor  Hu Li, Ph.D. , a Mayo Clinic Systems biology and AI researcher in the Department of Molecular Pharmacology and Experimental Therapeutics. "It has the potential to uncover insights missed by conventional AI."

Conventional AI is primarily used in classification and recognition tasks, such as face recognition and imaging classification in clinical diagnosis, and it has been increasingly applied to generative tasks, such as creating human-like text. Researchers note that conventional learning algorithms often do not incorporate existing scientific knowledge or hypotheses. Instead, these rely heavily on large, unbiased datasets, which can be challenging to obtain.

According to Dr. Li, this limitation considerably restricts the flexibility of AI methods and their uses in areas that demand knowledge discovery, like medicine.

AI is a valuable tool for identifying patterns in large and complex datasets like those employed in cancer research. The central challenge in using conventional AI has been maximizing the embedded information within those datasets.

"Lack of integration between existing knowledge and hypothesis can be a problem. AI models may produce results without careful design from researchers and clinicians what we refer to as the 'rubbish in rubbish out’ problem," says Dr. Li. "Without being guided by scientific questions, AI may provide less efficient analyses and struggle to yield significant insights that can help form testable hypotheses and move medicine forward."

With hypothesis-driven AI, researchers look to find ways to incorporate an understanding of a disease, for example, integrating known pathogenic genetic variants and interactions between certain genes in cancer into the design of the learning algorithm. This will enable researchers and clinicians to determine which components contribute to model performance and, hence, enhance interpretability. Further, this strategy can address dataset issues and promote our focus on open scientific questions.

"This new class of AI opens a new avenue for better understanding the interactions between cancer and the immune system and holds great promise not only to test medical hypotheses but also predict and explain how patients will respond to immunotherapies," says  Daniel Billadeau, Ph.D. , a professor in Mayo Clinic's Department of Immunology. Billadeau is a co-author and co-inventor of the study and has a long-standing research interest in cancer immunology, the study of how the body's immune system interacts with cancer.

The research team says hypothesis-driven AI can be used in all sorts of cancer research applications, including tumor classification, patient stratification, cancer gene discovery, drug response prediction and tumor spatial organization.

Benefits of hypothesis-driven AI:

• Targeted:  Focuses on specific hypotheses or research questions.
• Leverages existing knowledge:  Guides exploration to find previously missed connections.
• More interpretable:  Results are easier to understand than with conventional AI.
• Reduced resource needs:  Requires less data and computing power.
• "Machine-based reasoning":  Helps scientists test and validate hypotheses by incorporating hypotheses and biological and medical knowledge into the design of the learning algorithm.

Dr. Li notes that the disadvantage of this tool is that creating these types of algorithms requires expertise and specialized knowledge, potentially limiting wide accessibility. There is also potential for building in bias, and they say researchers must watch for that when applying different pieces of information. In addition, researchers generally have a limited scope and won't be formulating all possible scenarios, potentially missing some unforeseen and critical relationships.

"Nonetheless, hypothesis-driven AI facilitates active interactions between human experts and AI, that relieve the worries that AI will eventually eliminate some professional jobs," says Dr. Li.

Since hypothesis-driven AI is still in its infancy, questions remain, such as how to best integrate knowledge and biological information to minimize bias and improve interpretation. Dr. Li says despite the challenges, hypothesis-driven AI is a step forward.

"It can significantly advance medical research by leading to deeper understanding and improved treatment strategies, potentially charting a new roadmap to improve treatment regimens for patients," says Dr. Li.

Review the  study  for a complete list of authors, disclosures and funding.

A version of this article was originally published on the Mayo Clinic News Network .

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Unraveling the roles of non-coding DNA explains childhood cancer's resistance to chemotherapy

by St. Jude Children's Research Hospital

St. Jude Children's Research Hospital scientists have identified specific DNA variants in the non-coding regions of the genome contributing to chemotherapy resistance in acute lymphoblastic leukemia (ALL). The results guided the team to unravel the mechanism behind a previously unknown contributor to therapeutic resistance. The discovery was enabled by combining new technologies to overcome previous limitations in understanding the non-coding genome, which could be adapted to other types of cancer and diseases.

The findings are published in Nature Communications .

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Survival rates are over 94% due to modern therapy. However, those with relapsed or recurrent disease, often due to chemotherapy resistance , have a much poorer 30–40% survival rate.

The researchers studied resistance variants found in the non-coding genome, which makes up 98% of DNA and does not contain genes. Previous attempts to identify resistance mechanisms to chemotherapy had focused on DNA that encoded genes. Looking directly at genes is simpler because non-coding DNA can have complex relationships with gene function, but the St. Jude group has shown that it is possible.

"We demonstrated that we now have the tools to find relevant non-coding genetic factors that contribute to chemotherapy resistance," said corresponding author Daniel Savic, Ph.D., St. Jude Department of Pharmacy and Pharmaceutical Sciences. "The end goal is to understand the mechanisms of drug resistance so we can develop novel therapeutics and optimize existing chemotherapies based on the individual's unique genetic makeup."

Sorting through non-coding DNA to find the root of chemotherapy resistance

"The non-coding 98% of the genome contains instructions," said co-first author Jackson Mobley, Ph.D., St. Jude Department of Pharmacy and Pharmaceutical Sciences. "If we are making a building, genes encode the iron bars, wires and concrete; non-coding DNA are the blueprints. We found the small changes in the blueprints that impact how well you respond to certain therapies."

The group explored novel non-coding resistance variants by combining state-of-the-art technologies to examine patient samples and clinical data on treatment outcomes. In the past, research had focused on a single gene or variant. However, combining high-throughput DNA sequencing methods allowed the St. Jude researchers to perform massively parallel variant screens.

Those large screens enabled the testing of over 1,600 variants simultaneously to identify which were functional. That huge increase made the results more comprehensive, leading to the discovery of over 500 functional non-coding DNA variants associated with chemotherapy resistance.

"Our work represents the largest functional investigation of inherited non-coding variants associated with pharmacological traits, especially in ALL," said co-first author Kashi Raj Bhattarai, Ph.D., St. Jude Department of Pharmacy and Pharmaceutical Sciences. "We verified that identified variants also have a similar effect in cell lines and patient samples."

A novel resistance mechanism

By surveying many non-coding variants at once, the researchers were able to find the most impactful ones across different subtypes of ALL and connect them to a specific gene using innovative 3D genome mapping technologies. By finding the mechanism behind how variants in the non-coding genome affect target gene activity, they can figure out how it affects cancer's response to treatment.

For example, the top variant from the screen led to the discovery of a new resistance mechanism. The resistance was to the chemotherapy drug vincristine. The researchers examined how DNA containing the functional variant physically looped to its target gene and which transcription factors , proteins that guide gene expression, were involved.

The scientists found the variant bound near the gene for EIF3A, which is known to be involved in cell proliferation and survival. When they deleted the DNA containing the variant or reverted the mutation to the original sequence, they could alter the cells' sensitivity to the chemotherapeutic agent vincristine.

The study serves as a proof of principle of how to take non-coding DNA variants and mechanistically connect them to a trait, such as chemotherapy resistance. That has been a long-standing issue holding back genomics research on inherited variants, from cancer to neurological issues.

"In any genome-wide association study , nearly all associated variants reside in the non-coding genome," Savic said. "Therefore, connecting that variation to gene function and then to an actual trait, such as chemotherapy resistance or disease predisposition, is challenging. We showed that we have harnessed tools and technologies to systematically examine the non-coding genome and understand what it's doing. We hope that our findings can be utilized to improve clinical outcomes in ALL patients."

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Register for the oss 25th anniversary event, why do kids get cancer.

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I attended a seminar many years ago given by a Ph.D. student who had spent years working on a particular type of childhood cancer. During the question-and-answer period, I raised my hand. I wanted to know why it was that children even got cancer when most cancers require decades of mutation accumulation.

The student didn’t seem to understand my question, which I reformulated a couple of times before one of the professors in the audience turned to me and said, “It’s stochastic,” meaning it’s random, it can’t be predicted, and it’s just bad luck.

Let’s just say that I remained unsatisfied.

When adults get diagnosed with cancer, the question they often ask themselves is “why me?” But from a biological perspective, it’s not surprising. The way in which our cells divide requires so many moving parts that, once in a while, something is going to break down, leading to the uncontrolled cell growth characteristic of cancer. This breakdown takes decades. Yet, retinoblastoma, a tumour of the back of the eye that almost only affects children, usually gets diagnosed between the ages of one and two. How can cancer be a tortoise in adults but a hare in children?

The cancer ballet

Our bodies are made up of cells and these cells are not static. They will regularly duplicate their DNA content and split into two. This process, which is crucial to life, is very tightly regulated. It is called the cell cycle.

You can think of it as a wonderfully choreographed ballet involving hundreds of dancers—proteins, in the case of the cell cycle—and they all have a precise time to enter the stage, fulfill their role, and return behind the curtain. Day in, day out, proteins inside our cells perform  Swan Lake  over and over again, always hitting their mark. But sometimes, an important dancer is sick or is simply missing, and the choreography goes awry, more  Black Swan  than  Swan Lake . Over time, more and more dancers get sick and the whole production gets out of control. The troupe starts invading the seating area, recruiting members of the audience for their insubordinate dance, and the massive, incoherent ballet pours out of the theatre and disrupts city life.

This is cancer.

Proteins in cancer misbehave or simply disappear because the genes that produce them have been mutated. Exactly  when  those mutations happen has a direct influence on when someone develops cancer. In 1971, Alfred Knudson proposed a hypothesis for how mutations and cancer were linked. It is known as the two-hit hypothesis.

For cancer to start, the prima ballerina has to be taken out of commission. But, of course, she has an understudy. We have two copies of most genes, one from our father and one from our mother. If one copy is rendered useless, we still have the other copy to make a functional protein. This is what Knudson zeroed in on. He hypothesized, quite correctly, that in cancer, a mutation arises that inactivates the first copy of that gene. Later, a second mutation needs to hit that other copy. When both the prima ballerina and her understudy have been quashed, the ballet starts to lose control. (Analogies inevitably break down. There is no one prima ballerina in our cells, but many prima ballerinas—proteins that play key roles—and different cancers will emerge from the mutation of different key ballerinas.)

Knudson used retinoblastoma to make his point about his two-hit hypothesis. The gene  RB1  codes for the protein RB1, which acts as a necessary brake pedal in the cell cycle. When one copy of  RB1  is mutated and then, later, the second copy, the RB1 protein can no longer play its role and cells start to divide out of control. At this stage, we see a benign tumour called a retinoma. If more mutations start to happen to other important proteins, the child will develop retinoblastoma, an actual cancer of the retina.

A key to understanding cancer is that sometimes that first hit does not happen during the patient’s lifetime: sometimes, they have already inherited it from one of their parents. They are thus predisposed to developing cancer, and if they do get cancer they will typically be diagnosed at a much earlier age. This is why a 60-year-old woman presenting to a doctor with breast cancer will be seen as “normal,” but a 25-year-old woman presenting with the same will arouse suspicions that she inherited an important mutation from a parent. This is the difference between sporadic cancers, where both hits need to happen during the patient’s lifetime and thus often take decades, and inherited cancers, where only one important hit needs to happen during the patient’s lifetime and thus cancer arises earlier.

This model explains why  over half of all cancers  affect people older than 70 and why young adults with cancer will often be sent for genetic testing and counselling, because the mutation they inherited from a parent could further spread throughout the family. But it doesn’t explain why children develop cancer in the first place.

That is because their tumours tend to be very different from adult cancers.

Fewer mutations, fusion genes, and epigenetic alterations

Even without an understanding of the underlying genetics, we can simply look at the cancers that typically affect adults and children and notice that they are not the same.

Leukemias, which affect white blood cells, make up about a third of all cancers in children, but they are  12 th  in frequency  when looking at all age groups. The most common malignant brain tumour in children is medulloblastoma, which affects the back of the brain, but it is rarely found in adults. For glioblastoma, the opposite is true: common in adults but rare in children. Adults typically get diagnosed with breast, prostate, lung, or colorectal cancer. Children get afflicted by astrocytomas, leukemias, and osteosarcomas. Clearly, something different is happening here.

The first observation that comes out of the medical literature on pediatric cancers is that they have  fewer mutations  than adult tumours. In adults, the prima ballerina and her understudy are knocked out, and more and more ballet dancers subsequently stop doing their job. There is an accumulation of mutations in many genes, and that phenomenon both creates the cancer and helps it progress. In children, fewer mutations are needed to initiate cancer.

While all cancers feature mutations in important genes, the cancer-causing mutations that happen in children tend to be seen in genes that control progression through the cell cycle. The  RB1  gene is a perfect example. When absent, the cell cycle keeps going without regulation, with cells dividing and dividing and turning into tumours.

We also see  more fusion genes  in pediatric cancers versus adult cancers. A fusion gene is when one half of a gene gets combined with one half of another gene, creating a new protein that did not exist before. It may not seem like much, but when the first gene has a very important role to play intermittently and the second gene acts as a license to do it all the time, we end up with an overactive gene that favours the uncontrolled division of cells. It’s like installing a rocket engine at the back of a car and snipping the brake line during the fitting. The part-car, part-rocket vehicle will cause havoc on the highway.

Finally, childhood cancers differ from adult cancers not just genetically but also epigenetically. Genes make proteins but genes do not make proteins continually. Just like the cell cycle is tightly regulated, so is the production of proteins through gene expression. That process is known as epigenetic regulation, where “epigenetic” means “on top of the gene.” There are ways in which the genes are rendered inaccessible or silent, and it involves things like methylation and histones, and the genes coding for those very things are  often mutated  in childhood cancers. It means that gene expression is not as restrained as it should normally be, which leads to tumours forming faster.

These answers are helpful but they are not enough for us to fully understand what distinguishes pediatric cancers from adult ones. All of these peculiarities seem to interact and when they happen in the wrong cell at the wrong time of development, cancer follows.

With all of this talk of mutations driving cancer, you may be wondering how these mutations happen in the first place. Here too our understanding is incomplete. We know that certain behaviours in adults increase the risk of them developing cancer later in life, like smoking cigarettes and being exposed to ultraviolet radiation (such as the one found in sunlight) without protection. But children are too young for their behaviour to cause cancer at a young age. Certain viruses clearly cause cancer in adults, such as HPV resulting in cervical and anal cancer (among others). In children, some viruses  like the Epstein-Barr virus  have been shown to play a role in the development and progression of cancer, but our knowledge here is fragmentary.

Much like in adults, roughly  10%  of children with cancer are predisposed to it by inheriting a mutation from one of their parents. But as far as we know, everything else, as painful as it is to say, is stochastic. It is random, unpredictable, and just bad luck. Neither the parents nor the child is to blame.

Every year,  400,000  children and teenagers develop cancer worldwide. More research is definitely needed to further elucidate exactly why this happens and what we can do to help prevent it.

Take-home message: - The types of cancers that usually affect children are different than the types of cancers common in adults - Childhood cancers tend to require fewer mutations to develop; they often show fusion genes, in which parts of two different genes combine to create a protein that misbehaves; and they commonly show mutations in the molecules that regulate genes - As in adults, about one in ten children with cancer will have inherited a mutation from a parent that predisposes them to developing a tumour

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Investments in Basic Research for Pediatric Cancers: Developing Dinutuximab

NCI makes substantial investments in basic research, recognizing its fundamental importance in unraveling the complexities of pediatric cancers. A deeper understanding of cancer leads to new approaches for cancer prevention, screening, and treatment, like dinutuximab to treat neuroblastoma. Learn more about basic research in NCI’s Role in Cancer Research .

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Lyon Family Foundation supports pediatric cancer patients and families

• Sarah Sargent
• May 2, 2024

Racing to improve kids’ health

Prestigious award recognizes UChicago Medicine’s ‘high impact’ cancer research

Hyundai Hope on Wheels surpasses $250 million raised for pediatric cancer; survivor shares journey

CHICAGO (WLS) -- The continued fight to end childhood cancer is getting a boost.

Hyundai's Hope on Wheels has been fundraising for treatments and research since 1998.

ABC7 Chicago is now streaming 24/7. Click here to watch

The car maker has now surpassed $250 million in donations over the organizations' lifetime.

Some of that money has helped 11-year-old Bloomington native Oliver Foster.

When he was just five years old, he was diagnosed with acute lymphoblastic leukemia, a type of cancer of the blood and bone marrow.

His treatment lasted for three and a half years, and consisted of numerous chemo infusions, overnight stays at the hospital and 28 spinal taps.

John Guastaferro, executive director of Hope on Wheels, said the company has been able to help children like Foster through donations and contributions from Hyundai buyers.

SEE ALSO | Chicago boy battling leukemia becomes honorary CPD baseball team member, granted Disney World trip

"As a corporate foundation, all of our 840 Hyundai dealers across the nation are a part of this. Every time a car is sold, a portion goes into the foundation," Guastaferro said.

Most of the donations go towards funding research for pediatric cancer.

"This funding helps researchers and scientists discover new medical advances, find new cures, less invasive treatments and many other things," he said.

Foster's message to other children battling cancer is simple.

"It's okay to be scared, but that doesn't mean you can't be brave at the same time," he said.

For more information, or to make a donation, visit hyundaihopeonwheels.org .

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