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Toward a Drug Development Path That Targets Metastatic Progression in Osteosarcoma
Open accessAbstract
Despite successful primary tumor treatment, the development of pulmonary metastasis continues to be the most common cause of mortality in patients with osteosarcoma. A conventional drug development path requiring drugs to induce regression of established lesions has not led to improvements for patients with osteosarcoma in more than 30 years. On the basis of our growing understanding of metastasis biology, it is now reasonable and essential that we focus on developing therapeutics that target metastatic progression. To advance this agenda, a meeting of key opinion leaders and experts in the metastasis and osteosarcoma communities was convened in Bethesda, Maryland. The goal of this meeting was to provide a “Perspective” that would establish a preclinical translational path that could support the early evaluation of potential therapeutic agents that uniquely target the metastatic phenotype. Although focused on osteosarcoma, the need for this perspective is shared among many cancer types. The consensus achieved from the meeting included the following: the biology of metastatic progression is associated with metastasis-specific targets/processes that may not influence grossly detectable lesions; targeting of metastasis-specific processes is feasible; rigorous preclinical data are needed to support translation of metastasis-specific agents into human trials where regression of measurable disease is not an expected outcome; preclinical data should include an understanding of mechanism of action, validation of pharmacodynamic markers of effective exposure and response, the use of several murine models of effectiveness, and where feasible the inclusion of the dog with naturally occurring osteosarcoma to define the activity of new drugs in the micrometastatic disease setting. Clin Cancer Res; 20(16); 4200–9. ©2014 AACR.
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“The tendency for osteosarcoma to metastasize to the lung is an outcome-defining complication that drives patient mortality and challenges clinicians 50 .”
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Metadata
- Authors
- Khanna, C., Fan, T. M., Gorlick, R., Helman, L. J., Kleinerman, E. S., Adamson, P. C., Houghton, P. J., Tap, W. D., Welch, D. R., Steeg, P. S., Merlino, G., Sorensen, P. H. B., Meltzer, P., Kirsch, D. G., Janeway, K. A., Weigel, B., Randall, L., Withrow, S. J., Paoloni, M., Kaplan, R., Teicher, B. A., Seibel, N. L., Smith, M., Üren, A., Patel, S. R., Trent, J., Savage, S. A., Mirabello, L., Reinke, D., Barkaukas, D. A., Krailo, M., & Bernstein, M.
- Affiliations
- National Institutes of Health (US)
- University of Illinois Urbana-Champaign (US)
- Albert Einstein College of Medicine (US)
- 17Cancer Biology and
- Children's Hospital of Philadelphia (US)
- Nationwide Children's Hospital (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Kansas Medical Center (US)
- University of British Columbia (CA)
- Duke Medical Center (US)
- Harvard University (US)
- University of Minnesota (US)
- University of Utah (US)
- Colorado State University (US)
- Georgetown University Medical Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Translational Genomics Research Institute (US)
- University of Michigan (US)
- Children's Oncology Group (US)
- University of Southern California (US)
- Dalhousie University (CA)
- Corresponding author
- Fan, Timothy M.
- ORCID
- Fan, Timothy M.
- Gorlick, Richard
- Helman, Lee J.
- Kleinerman, Eugenie S.
- Adamson, Peter C.
- Houghton, Peter J.
- Tap, William D.
- Welch, Danny R.
- Steeg, Patricia S.
- Merlino, Glenn
- Sorensen, Poul H.B.
- Meltzer, Paul
- Kirsch, David G.
- Janeway, Katherine A.
- Weigel, Brenda
- Kaplan, Rosandra
- Teicher, Beverly A.
- Seibel, Nita L.
- Smith, Malcolm
- Üren, Aykut
- Patel, Shreyaskumar R.
- Trent, Jeffrey
- Savage, Sharon A.
- Mirabello, Lisa
- Reinke, Denise
- Krailo, Mark
- Bernstein, Mark
- Venue
- Clinical Cancer Research
- Published
- 2014-08-13
- Volume
- 20
- Issue
- 16
- Pages
- 4200-4209
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC4134738
- OpenAlex
- W1974879801
- Cited by
- 178
- References
- 66
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 25 · 2023: 13 · 2022: 6 · 2021: 23 · 2020: 22 · 2019: 13 · 2018: 16 · 2017: 7 · 2016: 20 · 2015: 18 · 2014: 2
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (ZIABC010566, U10-CA98543, U24CA114766, U10CA180899, U10CA180886, U10CA098543, P30CA016672)
- National Institute of Allergy and Infectious Diseases (K02AI093866)
- Topics
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Veterinary › Small Animals › Veterinary Oncology Research
- Keywords
- osteosarcoma, lung metastasis, metastatic progression, drug development, pharmacodynamic biomarkers, mouse model, micrometastatic disease, mechanism of action
- MeSH terms
- Animals, Antineoplastic Agents, Bone Neoplasms, Disease Models, Animal, Dogs, Drug Evaluation, Preclinical, Humans, Osteosarcoma, Disease Progression
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