摘要

       由于 Huggins 和 Hodges 最初观察到前列腺癌是雄激素依赖性的，因此雄激素消融疗法一直是治疗晚期前列腺癌 (CaP) 的金标准。雄激素受体 (AR) 被认为在 CaP 的发展和进展中起关键作用。新辅助、辅助和复发性疾病的治疗都集中在雄激素途径的调节和操作上，其中 AR 起着不可或缺的作用。最近发现 ETS 相关原癌基因的频繁过度表达可能是由 AR 驱动的，这是常见基因组重排的结果，这可能是了解前列腺癌早期阶段的关键。此外，AR 功能随着细胞向临床雄激素耗竭独立状态变化而发展。对 AR 功能、调节和异常的理解越来越细化，以了解 AR 在 CaP 和治疗应用中的作用。提高对 AR 及其网络在前列腺癌中的功能障碍的认识将有助于开发未来的 CaP 疗法。本综述重点关注 AR 的显着特征以及解决前列腺癌 AR 功能障碍的最新进展。

       Since the original observations of Huggins and Hodges that prostate cancers are androgen dependent, androgen ablation therapy has been the gold standard for the treatment of advanced prostate cancer (CaP). Androgen receptor (AR) is believed to play critical roles in the development and progression of CaP. Treatment for neoadjuvant, adjuvant and recurrent disease all center on the regulation and manipulation of the androgen pathway, in which AR plays an integral role. Recent discoveries that frequent overexpression of ETS-related proto-oncogenes may be driven by AR as a consequence of common genomic rearrangements can hold the key towards the understanding of early phases of prostate cancer. Furthermore, AR function evolves as the cell changes towards a clinically androgen depletion independent state. Comprehension of AR function, regulation and abnormalities are increasingly refined towards the understanding of the role of AR in CaP, and in therapeutic applications. Development of future therapy for CaP will be aided by improving the knowledge of dysfunctions of AR and its network in prostate cancer. This review focuses salient features of AR and on the recent advances addressing AR dysfunctions in prostate cancer.

https://www.nature.com/articles/4500936