Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group

Roberts, Ryan D.; Lizardo, Michael M.; Reed, Damon R.; Hingorani, Pooja; Glover, Jason; Allen‐Rhoades, Wendy; Fan, Timothy; Khanna, Chand; Sweet‐Cordero, E. Alejandro; Cash, Thomas; Bishop, Michael W.; Hegde, Meenakshi; Sertil, Aparna R.; Koelsche, Christian; Mirabello, Lisa; Malkin, David; Sorensen, Poul H.; Meltzer, Paul S.; Janeway, Katherine A.; Gorlick, Richard; Crompton, Brian D.

doi:10.1002/cncr.32351

Cited by 127Sarcoma Diagnosis and TreatmentBone Tumor Diagnosis and TreatmentsChromatin Remodeling and Cancer

Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group

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Roberts, Ryan D., Lizardo, Michael M., Reed, Damon R., Hingorani, Pooja, Glover, Jason, Allen‐Rhoades, Wendy, Fan, Timothy, Khanna, Chand +13 more·2019·Cancer

DOI 10.1002/cncr.32351PMC PMC6948723

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Abstract

Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more effective or less toxic regimens have proved disappointing. As we enter a postgenomic era in which we now recognize OS not as a cancer of mutations but as one defined by p53 loss, chromosomal complexity, copy number alteration, and profound heterogeneity, emerging threads of discovery leave many hopeful that an improving understanding of biology will drive discoveries that improve clinical care. Under the organization of the Bone Tumor Biology Committee of the Children's Oncology Group, a team of clinicians and scientists sought to define the state of the science and to identify questions that, if answered, have the greatest potential to drive fundamental clinical advances. Having discussed these questions in a series of meetings, each led by invited experts, we distilled these conversations into a series of seven Provocative Questions. These include questions about the molecular events that trigger oncogenesis, the genomic and epigenomic drivers of disease, the biology of lung metastasis, research models that best predict clinical outcomes, and processes for translating findings into clinical trials. Here, we briefly present each Provocative Question, review the current scientific evidence, note the immediate opportunities, and speculate on the impact that answered questions might have on the field. We do so with an intent to provide a framework around which investigators can build programs and collaborations to tackle the hardest problems and to establish research priorities for those developing policies and providing funding.

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Stratification systems that categorize patients by prognosis and/or osteosarcoma biology are currently being developed and validated.
“Stratification systems that categorize patients into subgroups based on prognosis and/or underlying osteosarcoma biology are currently being developed and validated 111 .”
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Abstract 3500: NCI's Provocative Questions Initiative
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[29]Wang LL, Levy ML, Lewis RA, Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet. 2001; 102(1): 11– 17. 11471165
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Authors: Roberts, R. D., Lizardo, M. M., Reed, D. R., Hingorani, P., Glover, J., Allen‐Rhoades, W., Fan, T., Khanna, C., Sweet‐Cordero, E. A., Cash, T., Bishop, M. W., Hegde, M., Sertil, A. R., Koelsche, C., Mirabello, L., Malkin, D., Sorensen, P. H., Meltzer, P. S., Janeway, K. A., Gorlick, R., & Crompton, B. D.
Affiliations: Nationwide Children's Hospital (US)
BC Cancer Agency (CA)
Moffitt Cancer Center (US)
Phoenix Children's Hospital (US)
Randall Children's Hospital at Legacy Emanuel (US)
Baylor College of Medicine (US)
University of Illinois Urbana-Champaign (US)
Ethos Vet Health Woburn Massachusetts
Division of Hematology and Oncology, Department of Pediatrics University of California San Francisco San Francisco California
Emory University (US)
St. Jude Children's Research Hospital (US)
University of Arizona (US)
Heidelberg University (DE)
National Institutes of Health (US)
University of Toronto (CA)
Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US)
The University of Texas MD Anderson Cancer Center (US)
Broad Institute (US)
Corresponding author: Crompton, Brian D.
ORCID: Roberts, Ryan D.
Lizardo, Michael M.
Reed, Damon R.
Hingorani, Pooja
Glover, Jason
Allen‐Rhoades, Wendy
Fan, Timothy
Bishop, Michael W.
Hegde, Meenakshi
Koelsche, Christian
Mirabello, Lisa
Malkin, David
Sorensen, Poul H.
Meltzer, Paul S.
Janeway, Katherine A.
Gorlick, Richard
Crompton, Brian D.
Venue: Cancer
Publisher: Wiley
Published: 2019-07-29
Volume: 125
Issue: 20
Pages: 3514-3525
ISSN: 0008-543X (ISSN-L)
1097-0142
DOI: 10.1002/cncr.32351
PMC: PMC6948723
OpenAlex: W2966831493
Cited by: 127
References: 92
Citations by year: 2026: 7 · 2025: 13 · 2024: 15 · 2023: 18 · 2022: 29 · 2021: 24 · 2020: 19 · 2019: 2
FWCI: 3.12
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Cancer (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (U10CA180886, K08CA188073, K08CA201638)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: osteosarcoma, p53 deficiency, copy number alterations, tumor heterogeneity, carcinogenesis, epigenomics, lung metastasis, preclinical models, translational research, research priorities, Children's Oncology Group
MeSH terms: Child, Humans, Mutation, Osteosarcoma, Tumor Suppressor Protein p53, Genomics, Proteomics, Translational Research, Biomedical, Epigenomics

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