alexa Androgen receptor antagonists in castration-resistant prostate cancer.

Author(s): Rathkopf D, Scher HI, Rathkopf D, Scher HI

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Abstract Persistent androgen receptor (AR) signaling despite low levels of serum androgens has been identified as a critical target for drug discovery in castration-resistant prostate cancer (CRPC). As proof of principle that the AR remains relevant in CRPC, 2 AR-targeted agents recently approved by the Food and Drug Administration-abiraterone and enzalutamide-have increased overall survival for patients with CRPC in the setting of prior chemotherapy. This review focuses on the AR and 2 direct antagonists, enzalutamide and ARN-509. These next-generation AR antagonists offer great promise for patients with advanced disease. Relative to conventional antiandrogens such as bicalutamide, they bind to the receptor with higher affinity, prevent nuclear translocation and DNA binding, and induce apoptosis without agonist activity in preclinical models. The success of these AR-targeted agents in the clinic has changed the landscape of therapy for patients with CRPC, and further therapeutic options building on this platform are currently in development.
This article was published in Cancer J and referenced in

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