Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer

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.

Indexed on Europe PMC as PubMed record 26563462 (DOI 10.1038/nrc4016). Its title names Androgen receptor and its text names Prostate cancer; PubMed types it as a review (Research Support, Non-U.S. Gov't, research-article, Review, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural). It was matched automatically to the idea "Destroy the truncated androgen receptor that hormone drugs cannot touch" and no figure has been checked by an editor.