Mechanisms of drug resistance that target the androgen axis in castration resistant prostate cancer (CRPC).
Mechanisms of drug resistance that target the androgen axis in castration resistant prostate cancer (CRPC).
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DOI：
10.1016/j.jsbmb.2015.05.010
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Penning TM
中科院分区：
文献类型：
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作者：
Penning TM
去势抵抗性前列腺癌（CRPC）是前列腺癌的致命形式，仍然依赖于雄激素。雄激素轴的再激活是由于肿瘤内的适应性雄激素生物合成，这可以由肾上腺雄激素和/或雄激素受体（AR）的变化（包括AR基因扩增）驱动。这些机制是针对P450c17抑制剂，如醋酸阿比特龙和AR超级拮抗剂，如恩杂鲁胺。临床经验表明，无论使用哪一种药物，最初的反应之后都是耐药性，患者在使用这些药物后会出现临床进展。本文综述了针对雄激素轴的内在和获得性耐药机制以及如何克服这一机制。
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. 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.