去势抵抗性前列腺癌（CRPC）由于其对传统雄激素受体（AR）靶向疗法的耐药性，给临床治疗带来了重大挑战。蛋白水解靶向嵌合体 (PROTAC) 的出现彻底改变了癌症治疗，能够靶向降解与 CRPC 进展有关的关键分子。在这篇综述中，我们讨论了用于 CRPC 治疗的 PROTAC 的发展，重点关注 AR 和其他 CRPC 相关调节剂。我们从靶向位点选择和临床前抗肿瘤评价等方面概述了AR PROTAC开发的战略趋势，以及AR降解剂在临床应用中的最新进展。此外，我们简要介绍了选择性 AR 降解剂开发的现状。此外，我们回顾了 PROTAC 作为潜在 CRPC 治疗范例的新进展，重点介绍了那些针对染色质调节剂 BRD4、EZH2 和 SWI/SNF 的药物；转录调节因子 SMAD3；以及激酶 CDK9 和 PIM1。鉴于 CRPC 和神经内分泌前列腺癌 (NEPC) 之间共有的分子靶标，我们还讨论了 PROTAC 在解决 NEPC 方面的潜力。

Castration-resistant prostate cancer (CRPC) presents significant challenges in clinical management due to its resistance to conventional androgen receptor (AR)-targeting therapies. The advent of proteolysis targeting chimeras (PROTACs) has revolutionized cancer therapy by enabling the targeted degradation of key molecular players implicated in CRPC progression. In this review we discuss the developments of PROTACs for CRPC treatment, focusing on AR and other CRPC-associated regulators. We provide an overview of the strategic trends in AR PROTAC development from the aspect of targeting site selection and preclinical antitumor evaluation, as well as updates on AR degraders in clinical applications. Additionally, we briefly address the current status of selective AR degrader development. Furthermore, we review new developments in PROTACs as potential CRPC treatment paradigms, highlighting those targeting chromatin modulators BRD4, EZH2, and SWI/SNF; transcription regulator SMAD3; and kinases CDK9 and PIM1. Given the molecular targets shared between CRPC and neuroendocrine prostate cancer (NEPC), we also discuss the potential of PROTACs in addressing NEPC.