Mechanisms of drug resistance that target the androgen axis in castration resistant prostate cancer (CRPC)

被引：42

作者：

Penning, Trevor M. ^{[1
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Ctr Excellence Environm Toxicol, Philadelphia, PA 19104 USA

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2015年 / 153卷

关键词：

Prostate cancer; Steroidogenesis; Androgen receptor; Therapeutics; RECEPTOR SPLICE VARIANTS; REMAINS HORMONE DRIVEN; I CLINICAL-TRIAL; ABIRATERONE ACETATE; ANTITUMOR-ACTIVITY; 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE; INTRATUMORAL ANDROGENS; INCREASED EXPRESSION; SELECTIVE INHIBITOR; DEPRIVATION THERAPY;

D O I：

10.1016/j.jsbmb.2015.05.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Castrate resistant prostate cancer (CRPC) is the fatal-form of prostate cancer and remains androgen dependent. The reactivation of the androgen axis occurs due to adaptive intratumoral androgen biosynthesis which can be driven by adrenal androgens and/or by changes in the androgen receptor (AR) including AR gene amplification. These mechanisms are targeted with P450c17 inhibitors e.g., abiraterone acetate and AR super-antagonists e.g., enzalutamide, respectively. Clinical experience indicates that with either agent an initial response is followed by drug resistance and the patient clinically progresses on these agents. This article reviews the mechanisms of intrinsic and acquired drug resistance that target the androgen axis and how this might be surmounted. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：105 / 113

页数：9

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