Chen Bo, Cao De-Hong, Guo Jian-Bing, Liu Liang-Ren, Wei Qiang
Department of Urology / Research Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Zhonghua Nan Ke Xue. 2019 Mar;25(3):265-271.
Prostate cancer is a most common malignant tumor in the male urogenital system. Currently, castration-resistant prostate cancer (CRPC) is a bottleneck in the treatment of prostate cancer, which has a very poor prognosis, with a median survival of merely 12 months. Although androgen-deprivation therapy eliminates the majority of the androgens in circulation, CRPC patients adapt to low-level androgens by synthesizing intratumoral androgens or altering androgen receptors. This review summarizes the main ways of synthesizing testosterone and dihydrotestosterone (DHT), the enzymes involved, and changes of the androgen level in different stages of CRPC. Blocking any one of the pathways of androgen biosynthesis is likely to upregulate another and lead to incomplete androgen elimination and consequently drug resistance. Therefore, identifying the pathways of androgen biosynthesis may provide an opportunity for the development of the drugs for blocking the major pathways of androgen and introtumoral androgen biosynthesis and antagonizing androgen receptors.
前列腺癌是男性泌尿生殖系统中最常见的恶性肿瘤。目前，去势抵抗性前列腺癌（CRPC）是前列腺癌治疗的一个瓶颈，其预后非常差，中位生存期仅为12个月。尽管雄激素剥夺疗法消除了循环中的大部分雄激素，但CRPC患者通过合成肿瘤内雄激素或改变雄激素受体来适应低水平雄激素。本文综述了睾酮和双氢睾酮（DHT）合成的主要途径、相关酶以及CRPC不同阶段雄激素水平的变化。阻断雄激素生物合成的任何一条途径都可能上调另一条途径，导致雄激素消除不完全，从而产生耐药性。因此，确定雄激素生物合成途径可能为开发阻断雄激素和肿瘤内雄激素生物合成主要途径以及拮抗雄激素受体的药物提供机会。
