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Cancer. 2019 Oct 15;125(20):3514-3525. doi: 10.1002/cncr.32351. Epub 2019 Jul 29.

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

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Center for Childhood Cancer, Nationwide Children's Hospital, The Ohio State University James Comprehensive Cancer Center, Columbus, Ohio.
Department of Molecular Oncology, BC Cancer, Provincial Health Services Authority, Vancouver, British Columbia, Canada.
Sarcoma Department, Chemical Biology and Molecular Medicine Program and Adolescent and Young Adult Oncology Program, Moffitt Cancer Center, Tampa, Florida.
Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, Arizona.
Children's Cancer and Blood Disorders Program, Randall Children's Hospital, Portland, Oregon.
Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas.
Texas Children's Hospital Cancer and Hematology Centers, Houston, Texas.
Department of Veterinary Clinical Medicine, University of Illinois, Urbana-Champaign, Illinois.
Ethos Vet Health, Woburn, Massachusetts.
Ethos Discovery (501c3), Washington, DC.
Division of Hematology and Oncology, Department of Pediatrics, University of California San Francisco, San Francisco, California.
Department of Pediatrics, Emory University, Children's Healthcare of Atlanta, Atlanta, Georgia.
Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Center for Cell and Gene Therapy, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
Department of Basic Medical Sciences, College of Medicine Phoenix, University of Arizona, Phoenix, Arizona.
Department of General Pathology, Institute of Pathology, Ruprecht-Karls-University, Heidelberg, Germany.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Pediatrics, Division of Hematology/Oncology, University of Toronto, Toronto, Ontario, Canada.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Dana-Farber Cancer Institute, Boston, and Broad Institute of Harvard and MIT, Cambridge, Massachusetts.


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.


osteosarcoma; pediatric oncology; program development; sarcoma; translational biology


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