文献类型：期刊文献

英文题名：Targeted therapies for urothelial carcinoma: From FGFR inhibitors to next-generation antibody-drug conjugates (Review)

作者：Du, Jinping[1,2];Shen, Hao[1,2];Zeng, Tongwei[1,2];Liu, Wei[1,2];Xie, Yongqiang[1,2]

第一作者：Du, Jinping

通信作者：Xie, YQ[1]

机构：[1]Gansu Univ Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Dept Urol, Affiliated Hosp 3, 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, Dept Urol, Affiliated Hosp 3, 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：2

外文期刊名：INTERNATIONAL JOURNAL OF ONCOLOGY

收录：;Scopus(收录号：2-s2.0-105026222990);WOS:【SCI-EXPANDED(收录号:WOS:001649863000001)】；

基金：Not applicable.

语种：英文

外文关键词：urothelial carcinoma; targeted therapy; fibroblast growth factor receptor inhibitors; antibody-drug conjugates; biomarkers; resistance mechanisms; precision medicine; therapeutic strategies

摘要：Treatment of urothelial carcinoma (UC), particularly in metastatic or cisplatin-ineligible patients, remains challenging because of limited durable responses to conventional chemotherapy and immune checkpoint inhibitors. Recent advances in targeted therapies, including FGFR inhibitors (for example, erdafitinib) and antibody-drug conjugates (ADCs) targeting Nectin-4 (enfortumab vedotin) and HER2 (disitamab vedotin), have reshaped treatment paradigms. FGFR3 alterations, which are present in 20-40% of patients with advanced UC, predict sensitivity to FGFR tyrosine kinase inhibitors, whereas ADCs demonstrate efficacy across biomarker-selected and unselected populations. However, clinical implementation is complicated by resistance mechanisms, such as kinase switching, phenotypic plasticity and tumor microenvironment interactions, as well as biomarker heterogeneity. The present review synthesizes current evidence on molecularly guided therapies, contrasts resistance mechanisms between FGFR inhibitors and ADCs, and evaluates strategies to overcome therapeutic limitations. By integrating translational insights and emerging preclinical data, it was aimed to provide a roadmap for optimizing biomarker-driven approaches, novel combinations and next-generation agents for the treatment of UC.