前列腺癌内分泌治疗抵抗机制的研究进展

Research progress on mechanisms of endocrine therapy resistance in prostate cancer

QI Zihao123，WANG Leijie2，WU Linjie3，BAl Xiaojie2，FAN Jiuming12， WANG Tiankun1.2， HAN Yutong1.2，

YU Ying3， GUO Zhongqiang3， ZENG Xiantao1.2.3

1.SchoolofClinical Medicine，HenanUniversity，Kaifeng 475oo4，HenanProvince，China

2.Center for Evidence-Based and Translational Medicine， Zhongnan Hospitalof Wuhan University，

Wuhan 430071， China

3.Department of Urology， Zhongnan Hospital of Wuhan University， Wuhan 430071， China

Corresponding authors： YU Ying， Email： 0oo33705@whu.edu.cn； GUO Zhongqiang， Email：

guozhongqiang@whu.edu.cn； ZENG Xiantao， Email： zengxiantaol128@163.com

【Abstract】Prostate cancer （PCa） is one of the most prevalent malignancies among men worldwide and a leading cause of cancer-related deaths. As an androgen-dependent tumor of the male reproductive system， PCa initially responds wellto androgen deprivation therapy （ADT） and second-generation androgen receptor （AR） antagonists （enzalutamide and apalutamide）， which significantly extend progression-free survival. However， Most patients would developed into castration-resistant prostate cancer（CRPC），resulting in the resistant to ADT.The mechanisms driving resistance to novel endocrine therapies exhibit biological complexity， includingabnormalities in the AR signaling axis，defects in DNA damage repair， alterations in the tumor microenvironment， and metabolic reprogramming. In recent years，important advances have been made in targeted therapeutic strategies.For instance，PARP inhibitors （olaparib） have demonstrated remarkable effcacy in patients with defects in DNA damage repair， PROTAC technology has shown potential in reversing castration resistance by degrading AR and its variants，thereby countering aberrant activation of the AR signaling pathway.This review systematically elucidates the major resistance mechanisms of CRPC，explores the latest advances in targeted and immunotherapy for CRPC，and envisions the potential of multidisciplinary， multi-target combination therapies to reverse castration resistance in PCa，providing novel therapeutic strategies and targets for CRPC.

【KeyWords】 Prostate cancer； Androgen receptor； Androgen deprivation therapy； Castration resistanceDrug resistance mechanism

前列腺癌（prostatecancer，PCa）是全球男性中发病率和死亡率最高的肿瘤之一，尤其在欧美国家，PCa已经成为仅次于肺癌的第二大致死性实体肿瘤[]。（剩余23346字）