Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer

被引:1128
作者
Watson, Philip A. [1 ]
Arora, Vivek K. [2 ]
Sawyers, Charles L. [1 ,3 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA
[2] Washington Univ, Sch Med, Div Med Oncol, St Louis, MO 63130 USA
[3] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
基金
美国国家卫生研究院;
关键词
SMALL-CELL CARCINOMA; BRCA MUTATION CARRIERS; ABIRATERONE ACETATE; SPLICE VARIANTS; POLY(ADP-RIBOSE) POLYMERASE; PROGESTERONE-RECEPTOR; WITHDRAWAL SYNDROME; ANTITUMOR-ACTIVITY; MOLECULAR CHARACTERIZATION; SELECTIVE-INHIBITION;
D O I
10.1038/nrc4016
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:701 / 711
页数:11
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