Toward a drug development path that targets metastatic progression in osteosarcoma

Chand Khanna, Timothy M. Fan, Richard Gorlick, Lee J. Helman, Eugenie S. Kleinerman, Peter C. Adamson, Peter J. Houghton, William D. Tap, Danny R. Welch, Patricia S. Steeg, Glenn Merlino, Poul H B Sorensen, Paul Meltzer, David G. Kirsch, Katherine A. Janeway, Brenda Weigel, Lor Randall, Stephen J. Withrow, Melissa Paoloni, Rosandra Kaplan & 12 others Beverly A. Teicher, Nita L. Seibel, Malcolm Smith, Aykut Üren, Shreyaskumar R. Patel, Jeffrey Trent, Sharon A. Savage, Lisa Mirabello, Denise Reinke, Donald A. Barkaukas, Mark Krailo, Mark Bernstein

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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 fromthe 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.

Original languageEnglish (US)
Pages (from-to)4200-4209
Number of pages10
JournalClinical Cancer Research
Volume20
Issue number16
DOIs
StatePublished - Aug 15 2014

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Osteosarcoma
Neoplasm Metastasis
Pharmaceutical Preparations
Expert Testimony
Neoplasms
Therapeutics
Dogs
Phenotype
Lung
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Khanna, C., Fan, T. M., Gorlick, R., Helman, L. J., Kleinerman, E. S., Adamson, P. C., ... Bernstein, M. (2014). Toward a drug development path that targets metastatic progression in osteosarcoma. Clinical Cancer Research, 20(16), 4200-4209. https://doi.org/10.1158/1078-0432.CCR-13-2574

Toward a drug development path that targets metastatic progression in osteosarcoma. / Khanna, Chand; 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; Randall, Lor; Withrow, Stephen J.; Paoloni, Melissa; Kaplan, Rosandra; Teicher, Beverly A.; Seibel, Nita L.; Smith, Malcolm; Üren, Aykut; Patel, Shreyaskumar R.; Trent, Jeffrey; Savage, Sharon A.; Mirabello, Lisa; Reinke, Denise; Barkaukas, Donald A.; Krailo, Mark; Bernstein, Mark.

In: Clinical Cancer Research, Vol. 20, No. 16, 15.08.2014, p. 4200-4209.

Research output: Contribution to journalArticle

Khanna, C, Fan, TM, Gorlick, R, Helman, LJ, Kleinerman, ES, Adamson, PC, Houghton, PJ, Tap, WD, Welch, DR, Steeg, PS, Merlino, G, Sorensen, PHB, Meltzer, P, Kirsch, DG, Janeway, KA, Weigel, B, Randall, L, Withrow, SJ, Paoloni, M, Kaplan, R, Teicher, BA, Seibel, NL, Smith, M, Üren, A, Patel, SR, Trent, J, Savage, SA, Mirabello, L, Reinke, D, Barkaukas, DA, Krailo, M & Bernstein, M 2014, 'Toward a drug development path that targets metastatic progression in osteosarcoma', Clinical Cancer Research, vol. 20, no. 16, pp. 4200-4209. https://doi.org/10.1158/1078-0432.CCR-13-2574
Khanna C, Fan TM, Gorlick R, Helman LJ, Kleinerman ES, Adamson PC et al. Toward a drug development path that targets metastatic progression in osteosarcoma. Clinical Cancer Research. 2014 Aug 15;20(16):4200-4209. https://doi.org/10.1158/1078-0432.CCR-13-2574
Khanna, Chand ; 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 ; Randall, Lor ; Withrow, Stephen J. ; Paoloni, Melissa ; Kaplan, Rosandra ; Teicher, Beverly A. ; Seibel, Nita L. ; Smith, Malcolm ; Üren, Aykut ; Patel, Shreyaskumar R. ; Trent, Jeffrey ; Savage, Sharon A. ; Mirabello, Lisa ; Reinke, Denise ; Barkaukas, Donald A. ; Krailo, Mark ; Bernstein, Mark. / Toward a drug development path that targets metastatic progression in osteosarcoma. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 16. pp. 4200-4209.
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