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MET and VEGF: synergistic targets in castration-resistant prostate cancer

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  • Molecular and Cellular Biology of Cancer
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Abstract

Recent advances in the treatment of prostate cancer have resulted in improved outcomes, including longer survival, but new options are needed for treating patients with castration-resistant disease, particularly in the presence of bone metastasis. Data from preclinical models and clinical biomarker studies indicate that antiangiogenic agents should be a promising treatment for this patient population, and multiple agents in this class have demonstrated activity in early-stage clinical trials. Pivotal trials in prostate cancer with agents targeting vascular endothelial growth factor (VEGF) signalling have resulted in significant improvements in tumour response and progression-free survival. However, overall survival was not significantly improved. Recent preclinical studies suggest that the limited impact on overall survival may result from the development of evasive resistance after inhibition of angiogenesis, possibly through upregulation of MET (hepatocyte growth factor receptor) signalling. MET plays important roles in angiogenesis, tumour cell invasion and bone metastasis, all of which are key factors in castration-resistant prostate cancer. Inhibition of both the MET and VEGF pathways may improve the efficacy of angiogenesis inhibitors in prostate cancer.

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  1. Exelixis, Inc., 210 East Grand Avenue, South San Francisco, CA, 94083-0511, USA

    Dana T. Aftab

  2. Comprehensive Cancer Center Cardiovascular Research Institute and Department of Anatomy, University of California-San Francisco, San Francisco, CA, USA

    Donald M. McDonald

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Aftab, D.T., McDonald, D.M. MET and VEGF: synergistic targets in castration-resistant prostate cancer. Clin Transl Oncol 13, 703–709 (2011). https://doi.org/10.1007/s12094-011-0719-5

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