Solid Tumour Target Discovery Laboratory, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Department of Pharmacy, No.921 Hospital of the Joint Logistics Support Force, Changsha, 410003, China.
Clin Transl Oncol. 2023 Feb;25(2):352-363. doi: 10.1007/s12094-022-02957-x. Epub 2022 Oct 6.
Androgen receptor (AR) plays a vital role in prostate cancer (PCa), including castration-resistant PCa, by retaining AR signalling. Androgen deprivation treatment (ADT) has been the standard treatment in the past decades. A great number of AR antagonists initially had been found effective in tumour remission; however, most PCa relapsed that caused by pre-translational resistance such as AR mutations to turn antagonist into agonist, and AR variants to bypass the androgen binding. Recently, several alternative therapeutic choices have been proposed. Among them, proteolysis targeting chimera (PROTAC) acts different from traditional drugs that usually function as inhibitors or antagonists, and it degrades oncogenic protein and does not disrupt the transcription of an oncogene. This review first discussed some essential mechanisms of ADT resistance, and then introduced the application of AR-targeted PROTAC in PCa cells, as well as other AR-targeted therapeutic choices.
雄激素受体（AR）在前列腺癌（PCa）中发挥着至关重要的作用，包括去势抵抗性 PCa，通过保留 AR 信号。雄激素剥夺治疗（ADT）在过去几十年一直是标准治疗方法。大量的 AR 拮抗剂最初被发现对肿瘤缓解有效；然而，大多数 PCa 复发是由于预翻译抵抗引起的，例如 AR 突变将拮抗剂转化为激动剂，以及 AR 变体绕过雄激素结合。最近，已经提出了几种替代治疗选择。其中，蛋白水解靶向嵌合体（PROTAC）的作用不同于传统药物，传统药物通常作为抑制剂或拮抗剂发挥作用，它降解致癌蛋白，并且不会破坏致癌基因的转录。本文首先讨论了 ADT 抵抗的一些基本机制，然后介绍了 AR 靶向 PROTAC 在 PCa 细胞中的应用，以及其他 AR 靶向治疗选择。
