文献类型：期刊文献

英文题名：Novel therapeutic strategies for metastatic castration-resistant prostate cancer: Beyond androgen receptor pathway inhibition (Review)

作者：Wang, Yaqin[1];Xie, Yongqiang[2];Zhao, Qiang[2]

第一作者：王玉琴;王引权

通信作者：Xie, YQ[1];Zhao, Q[1]

机构：[1]Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Oncol, Baiyin 730900, Gansu, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Affiliated Hosp 3, Dept Urol, 222 Silong Rd, Baiyin 730900, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Tradit Chinese Med, Affiliated Hosp 3, Dept Urol, 222 Silong Rd, Baiyin 730900, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：68

期号：6

外文期刊名：INTERNATIONAL JOURNAL OF ONCOLOGY

收录：;Scopus(收录号：2-s2.0-105035732089);WOS:【SCI-EXPANDED(收录号:WOS:001752835200001)】；

语种：英文

外文关键词：metastatic castration-resistant prostate cancer; poly (ADP-ribose) polymerase inhibitors; prostate-specific membrane antigen theranostics; protein kinase B blockade; CDK12 loss; bispecific antibodies; antibody-drug conjugates

摘要：Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to universal resistance to androgen-receptor pathway inhibitors (ARPI). Tumor progression is orchestrated by a spectrum of androgen-receptor-independent drivers, including genomic alterations in DNA damage repair pathways, epigenetic shifts promoting lineage plasticity, metabolic adaptations and an immunosuppressive tumor microenvironment. This evolving understanding has catalyzed the development of novel therapeutic strategies. These include PARP inhibitors for tumors with homologous recombination repair deficiencies, protein kinase B inhibitors for the phosphatase and tensin homolog-loss subset, prostate-specific membrane antigen (PSMA)-targeted radioligand therapy, bispecific T-cell engagers, antibody-drug conjugates and immune checkpoint inhibitors. Furthermore, liquid biopsy profiling, PSMA-positron emission tomography-based radiomics and artificial intelligence platforms are enhancing real-time patient selection and response assessment. The present review synthesized these recent preclinical and clinical advances to delineate biomarker-driven, mechanism-based therapeutic sequencing and combination strategies for mCRPC in the post-ARPI era.