Anti-androgens and androgen-depleting therapies in prostate cancer: new agents for an established target

被引：236

作者：

Chen, Yu ^{[2
,3
]}

Clegg, Nicola J. ^{[2
,3
]}

Scher, Howard I. ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

来源：

LANCET ONCOLOGY | 2009年 / 10卷 / 10期

关键词：

STRUCTURAL BASIS; ANTIANDROGEN WITHDRAWAL; ABIRATERONE ACETATE; RECEPTOR MUTATIONS; CONTROLLED-TRIAL; BINDING DOMAIN; PHASE-III; BICALUTAMIDE; CASTRATION; FLUTAMIDE;

D O I：

10.1016/S1470-2045(09)70229-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Activation of the androgen receptor is crucial for prostate cancer growth at all points of the illness. Current therapies targeting the androgen receptor, including androgen-depletion approaches and anti-androgens, do not completely inhibit the receptor activity. Prostate cancer cells develop resistance to castration by acquiring changes that include androgen-receptor overexpression and overexpression of enzymes involved in androgen biosynthesis, which result in reactivation of the receptor. Based on an understanding of these resistance mechanisms and androgen biosynthesis pathways, new anti-androgens and androgen-depleting agents have been developed. Notably, promising activity has been shown in early phase trials by MDV3100, a new anti-androgen designed for activity in prostate cancer model systems with overexpressed androgen receptor, and by abiraterone acetate, a CYP17A inhibitor that blocks steroid biosynthesis in the adrenal gland and possibly within the tumour. Both agents are undergoing phase 3 testing. Here, we review the basic science and clinical development of these and other agents.

引用

页码：981 / 991

页数：11

共 76 条

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