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26-04-2016 | Genitourinary cancers | Book chapter | Article

10. Enzalutamide in Metastatic Castration Resistant Prostate Cancer

Authors: Jeffrey Shevach, Bridget K. Marcellino, William K. Oh, Che-Kai Tsao

Publisher: Springer International Publishing

Abstract

Historically metastatic castration resistant prostate cancer (mCRPC), a lethal disease phenotype with disease progression despite androgen deprivation, was thought to be truly “hormonal refractory.” However, recent approval of novel of androgen receptor signaling inhibitors based on definitive survival benefit provides proof of the principle that prostate cancer growth and progression remains critically dependent on this pathway. One such therapy is enzalutamide. Formerly known as MDV3100, enzalutamide was selected for development specifically because of its ability to induce tumor death in castration resistant prostate cancer in preclinical models. After demonstrating favorable clinical efficacy and safety profiles in two large randomized phase III studies, enzalutamide is now approved for treatment of patients with mCRPC, either in docetaxel-naïve or -resistant disease. Despite its effectiveness, resistance ultimately develops for most, and several resistance mechanisms involving the androgen-signaling pathway have been identified. Moreover, the optimal use of enzalutamide therapy is yet undefined. Continued investigation of enzalutamide resistance pathways will be key in the development of novel treatments in this lethal disease.

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