Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer

Philip A. Watson, Vivek K. Arora, Charles L. Sawyers

Research output: Contribution to journalReview articlepeer-review

697 Scopus citations

Abstract

During the past 10 years, preclinical studies implicating sustained androgen receptor (AR) signalling as the primary driver of castration-resistant prostate cancer (CRPC) have led to the development of novel agents targeting the AR pathway that are now in widespread clinical use. These drugs prolong the survival of patients with late-stage prostate cancer but are not curative. In this Review, we highlight emerging mechanisms of acquired resistance to these contemporary therapies, which fall into the three broad categories of restored AR signalling, AR bypass signalling and complete AR independence. This diverse range of resistance mechanisms presents new challenges for long-term disease control, which may be addressable through early use of combination therapies guided by recent insights from genomic landscape studies of CRPC.

Original languageEnglish
Pages (from-to)701-711
Number of pages11
JournalNature Reviews Cancer
Volume15
Issue number12
DOIs
StatePublished - Nov 24 2015

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