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Management of Castration Resistant Prostate Cancer pp 265–276Cite as

Targeting C-Met/VEGF in Castration Resistant Prostate Cancer

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Part of the book series: Current Clinical Urology ((CCU))

Abstract

HGF/MET and VEGF/VEGFR pathways have emerged as rational therapeutic targets in castrate-resistant prostate cancer (CRPC). Preclinical studies support the role of inhibition of these pathways in this challenging disease. Clinical trials using agents that inhibit either one but not both pathways concurrently suggest modest activity with no overall survival benefit. Cabozantinib (Cabo) is a multi-targeted tyrosine kinase inhibitor against MET, VEGFR2, RET. A phase II randomized discontinuation trial in patients with metastatic CRPC showed significant improvement in bone scans, bone turnover markers, and pain response. However, Cabo was associated with significant adverse events resulting in dose reduction and treatment discontinuation. Ongoing phase II and two phase III trials are expected to define the role of Cabo in CRPC. The development of biomarkers predictive of response will further refine the role of targeted therapies in the management of CRPC.

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Authors and Affiliations

  1. Department of Internal Medicine (Hematology/Oncology), University of Michigan, C353 Med Inn Bldg. SPC 5848, 1500 E. Medical Center Dr, Ann Arbor, MI, 48109-5848, USA

    Petros D. Grivas MD, PhD

  2. Department of Internal Medicine, University of Michigan, 7302 CC SPC 5948, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109-5948, USA

    David C. Smith MD

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Correspondence to David C. Smith MD .

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  1. Department of Surgery, University of Montreal Hospital Center, Montreal, Québec, Canada

    Fred Saad

  2. Department of Oncology, The Johns Hopkins University, Baltimore, Maryland, USA

    Mario A. Eisenberger

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Grivas, P.D., Smith, D.C. (2014). Targeting C-Met/VEGF in Castration Resistant Prostate Cancer. In: Saad, F., Eisenberger, M. (eds) Management of Castration Resistant Prostate Cancer. Current Clinical Urology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1176-9_19

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