FGFR3 alterations in bladder cancer:Sensitivity and resistance to targeted therapies  

作　　者：Maxim Noeraparast Katarina Krajina Renate Pichler Dora Nieders-Beke Shahrokh F Shariat Viktor Grünwald Sascha Ahyai Martin Pichler 

机构地区：[1]Translational Oncology,II.Med Clinics Hematology and Oncology,Augsburg,Germany [2]Department of Urology,Medical University of Innsbruck,Innsbruck,Austria [3]Department of Hematology and Oncology,Clinics Ottakring,Vienna,Austria [4]Department of Urology,Medical University of Vienna,Vienna,Austria [5]Interdisciplinary Genitourinary Oncology,Clinic for Urology,Clinic for Medical Oncology,University Hospital Essen,Hufelandstrase 55,Essen,Germany [6]Department of Urology,Medical University of Graz,Graz,Austria

出　　处：《Cancer Communications》2024年第10期1189-1208,共20页癌症通讯（英文）

摘　　要：In this review,we revisit the pivotal role of fibroblast growth factor receptor 3(FGFR3)in bladder cancer(BLCA),underscoring its prevalence in both nonmuscle-invasive and muscle-invasive forms of the disease.FGFR3 mutations in up to half of BLCAs play a well-established role in tumorigenesis,shaping distinct tumor initiation patterns and impacting the tumor microenvironment(TME).Emphasizing the importance of considering epithelial-mesenchymal transition profile and TME status,we revisit their relevance in predicting responses to immune checkpoint inhibitors in FGFR3-mutated BLCAs.This writing highlights the initially promising yet transient efficacy of the FGFR inhibitor Erdafitinib on FGFR3-mutated BLCA,stressing the pressing need to unravel resistance mechanisms and identify co-targets for future combinatorial studies.A thorough analysis of recent preclinical and clinical evidence reveals resistance mechanisms,including secondarymutations,epigenetic alterations in pathway effectors,phenotypic heterogeneity,and population-specific variations within FGFR3 mutational status.Lastly,we discuss the potential of combinatorial treatments and concepts like synthetic lethality for discovering more effective targeted therapies against FGFR3-mutated BLCA.

关 键 词：Bladder Cancer Erdafitinib FGFR inhibition FGFR3 mutations Resistance to Erdafitinib Tumor Microenvironment 

分 类 号：R737.14[医药卫生—肿瘤]