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Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group
Open accessAbstract
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 into subgroups based on prognosis and/or underlying osteosarcoma biology are currently being developed and validated 111 .”
From Osteosarcoma (2022) · cites this paper as [111]
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Metadata
- 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
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2019-07-29
- Volume
- 125
- Issue
- 20
- Pages
- 3514-3525
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- 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
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (U10CA180886, K08CA188073, K08CA201638)
- Topics
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Orthopedics and Sports Medicine › 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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