Emerging Mechanisms of Enzalutamide Resistance in Prostate Cancer

Overview

Journal Nat Rev Urol

Specialty Urology

Date 2014 Sep 17

PMID 25224448

Citations 73

Authors

Frank Claessens

Christine Helsen

Stefan Prekovic

Thomas Van den Broeck

Lien Spans

Hendrik van Poppel

Steven Joniau

Affiliations

Soon will be listed here.

Abstract

The majority of prostate cancers are hormone-dependent at diagnosis highlighting the central role of androgen signalling in this disease. Surprisingly, most forms of castration-resistant prostate cancer (CRPC) are still dependent on the androgen receptor (AR) for survival. Therefore, the advent of new AR-targeting drugs, such as enzalutamide, is certainly beneficial for the many patients with metastatic CRPC. Indeed, this compound provides a substantial survival benefit-but it is not curative. This Perspectives article describes the different ways through which cancer cells can become resistant to enzalutamide, such as AR truncation and other mutations, as well as by-pass of the AR dependence of prostate cancer cells through expression of the glucocorticoid receptor. The clinical relevance of these mechanisms and emerging questions concerning new therapeutic regimens in the treatment of metastatic CRPC are being discussed.

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