Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.
Departments of Pathology and Urology, George Whipple Lab for Cancer Research, University of Rochester Medical Center, Rochester, NY 14642, USA.
Cancer Lett. 2017 Jul 1;397:133-143. doi: 10.1016/j.canlet.2017.03.022. Epub 2017 Mar 18.
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941. Multiple strategies related to surgical/chemical castration with combinations of various anti-androgens, including Cyproterone Acetate, Flutamide, Nilutamide, Bicalutamide (Casodex) and Enzalutamide, as well as some androgen synthesis blockers, including Abiraterone, have been used to control PCa progression. However, patients on ADT with anti-androgen treatment eventually develop resistance, which might be accompanied with the unwanted side effects of enhanced metastasis. New therapeutic approaches via directly targeting the AR with ASC-J9, Cisplatin, EPI-001, Niclosamide, and VPC compounds as well as silencing AR with siRNAs or non-coding RNAs have been developed to further suppress PCa at the castration resistant stages.
前列腺癌（PCa）是美国男性癌症相关死亡的第二大原因，其进展与雄激素/雄激素受体（AR）信号密切相关。青春期前被阉割的男性（太监）或患有 II 型 5α-还原酶遗传缺陷（无法将睾酮转化为更有效的二氢睾酮）（DHT）的男性不会患上 PCa。迄今为止，自 1941 年 Huggins 和 Hodges 发现以来，雄激素剥夺疗法（ADT）联合抗雄激素治疗以减少或防止雄激素与 AR 结合，仍然是治疗晚期 PCa 的主要选择。多种与手术/化学阉割相关的策略，包括醋酸环丙孕酮、氟他胺、尼鲁米特、比卡鲁胺（卡索德克斯）和恩扎卢胺，以及一些雄激素合成抑制剂，如阿比特龙，已被用于控制 PCa 的进展。然而，接受 ADT 联合抗雄激素治疗的患者最终会产生耐药性，这可能伴随着增强转移的不良副作用。通过直接靶向 AR 的 ASC-J9、顺铂、EPI-001、尼克罗米德和 VPC 化合物以及使用 siRNA 或非编码 RNA 沉默 AR 的新治疗方法已被开发用于进一步抑制去势抵抗阶段的 PCa。
