Prostate cancer (PCa) affects millions of men globally. Due to advances in understanding genomic landscapes and biological functions, the treatment of PCa continues to improve. Recently, various new classes of agents, which include next-generation androgen receptor (AR) signaling inhibitors (abiraterone, enzalutamide, apalutamide, and darolutamide), bone-targeting agents (radium-223 chloride, zoledronic acid), and poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib, rucaparib, and talazoparib) have been developed to treat PCa. Agents targeting other signaling pathways, including cyclin-dependent kinase (CDK)4/6, Ak strain transforming (AKT), wingless-type protein (WNT), and epigenetic marks, have successively entered clinical trials. Furthermore, prostate-specific membrane antigen (PSMA) targeting agents such as ¹⁷⁷Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic efficacy. Advanced clinical studies with immune checkpoint inhibitors (ICIs) have shown limited benefits in PCa, whereas subgroups of PCa with mismatch repair (MMR) or CDK12 inactivation may benefit from ICIs treatment. In this review, we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms, and further discussed their limitations and future directions.

前列腺癌 (PCa) 影响全球数百万男性。由于对基因组景观和生物学功能的理解取得了进展，PCa 的治疗继续得到改善。最近，各种新型药物，包括下一代雄激素受体 (AR) 信号抑制剂（阿比特龙、恩杂鲁胺、阿帕鲁胺和 darolutamide）、骨靶向剂（氯化镭 223、唑来膦酸）和聚 (ADP-核糖）聚合酶（PARP）抑制剂（olaparib、rucaparib和talazoparib）已被开发用于治疗PCa。针对其他信号通路的药物，包括细胞周期蛋白依赖性激酶（CDK）4/6、Ak应变转化（AKT）、无翼型蛋白（WNT）和表观遗传标记，已陆续进入临床试验。此外，前列腺特异性膜抗原 (PSMA) 靶向剂，例如¹⁷⁷Lu-PSMA-617 是很有前途的治疗诊断学，可以提高诊断准确性和治疗效果。免疫检查点抑制剂 (ICIs) 的高级临床研究显示 PCa 的益处有限，而具有错配修复 (MMR) 或 CDK12 失活的 PCa 亚组可能受益于 ICIs 治疗。在这篇综述中，我们总结了临床试验中 PCa 的靶向药物及其潜在机制，并进一步讨论了它们的局限性和未来的发展方向。