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Nat Rev Cancer. 2015 Dec;15(12):701-11. doi: 10.1038/nrc4016. Epub 2015 Nov 13.

Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer.

Author information

1
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
2
Division of Medical Oncology, Washington University School of Medicine, St Louis, Missouri 63130, USA.
3
Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.

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.

PMID:
26563462
PMCID:
PMC4771416
DOI:
10.1038/nrc4016
[Indexed for MEDLINE]
Free PMC Article

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