Department of Urology, Peking University People's Hospital, Beijing 100044, China; The Institute of Applied Lithotripsy Technology, Peking University, Beijing 100044, China.
Department of Urology, Peking University People's Hospital, Beijing 100044, China; The Institute of Applied Lithotripsy Technology, Peking University, Beijing 100044, China.
Pharmacol Res. 2024 Jul;205:107230. doi: 10.1016/j.phrs.2024.107230. Epub 2024 May 22.
Immune checkpoint inhibitors (ICIs) are essential for urothelial carcinoma (UC) treatment. Fibroblast growth factor receptor (FGFR) alterations, as common oncogenic drivers in UC, have been reported to drive T cell depletion of UC immune microenvironment via up-regulating FGFR signaling, which indicated FGFR alterations potentially result in reduced response to ICIs. In addition, the selective pan-FGFR inhibitor showed better clinical benefit in clinical trials, indicating FGFR has emerged as critical therapeutic target via inhibiting FGFR signaling. The present study aims to evaluate prognosis and response to ICIs between FGFR-altered UC patients and FGFR-wildtype UC patients via 1963 UC patients and offers new insights into personalized precision therapy and combination therapy for UC.
免疫检查点抑制剂(ICIs)是治疗尿路上皮癌(UC)的关键。成纤维细胞生长因子受体(FGFR)改变作为 UC 常见的致癌驱动因素,已被报道通过上调 FGFR 信号通路导致 UC 免疫微环境中的 T 细胞耗竭,这表明 FGFR 改变可能导致对 ICI 的反应降低。此外,选择性泛 FGFR 抑制剂在临床试验中显示出更好的临床获益,表明通过抑制 FGFR 信号通路,FGFR 已成为关键的治疗靶点。本研究旨在通过 1963 例 UC 患者评估 FGFR 改变的 UC 患者与 FGFR 野生型 UC 患者的预后和对 ICI 的反应,为 UC 的个体化精准治疗和联合治疗提供新的见解。