Toward a Drug Development Path That Targets Metastatic Progression in Osteosarcoma

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 patie...

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Bibliographic Details
Published in:	Clinical cancer research Vol. 20; no. 16; pp. 4200 - 4209
Main Authors:	KHANNA, Chand, FAN, Timothy M, MERLINO, Glenn, SORENSEN, Poul H. B, MELTZER, Paul, KIRSCH, David G, JANEWAY, Katherine A, WEIGEL, Brenda, RANDALL, Lor, WITHROW, Stephen J, PAOLONI, Melissa, KAPLAN, Rosandra, GORLICK, Richard, TEICHER, Beverly A, SEIBEL, Nita L, SMITH, Malcolm, UREN, Aykut, PATEL, Shreyaskumar R, TRENT, Jeffrey, SAVAGE, Sharon A, MIRABELLO, Lisa, REINKE, Denise, BARKAUKAS, Donald A, HELMAN, Lee J, KRAILO, Mark, BERNSTEIN, Mark, KLEINERMAN, Eugenie S, ADAMSON, Peter C, HOUGHTON, Peter J, TAP, William D, WELCH, Danny R, STEEG, Patricia S
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 15-08-2014
Subjects:	Animals Antineoplastic agents Antineoplastic Agents - therapeutic use Biological and medical sciences Bone Neoplasms - drug therapy Bone Neoplasms - pathology Disease Models, Animal Disease Progression Diseases of the osteoarticular system Dogs Drug Evaluation, Preclinical Humans Medical sciences Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Osteosarcoma - drug therapy Osteosarcoma - secondary Pharmacology. Drug treatments Tumors Tumors of striated muscle and skeleton Drug Targeting Sarcoma Diseases of the osteoarticular system Malignant tumor Metastasis Research and development Osteoarticular system Target Osteosarcoma Advanced stage Bone Cancer
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.CCR-13-2574