在这篇综述中，我们重新审视了成纤维细胞生长因子受体 3 (FGFR3) 在膀胱癌 (BLCA) 中的关键作用，强调了其在非肌肉侵袭性和肌肉侵袭性疾病中的患病率。多达一半的 BLCA 中的 FGFR3 突变在肿瘤发生中发挥着明确的作用，形成独特的肿瘤起始模式并影响肿瘤微环境 (TME)。强调考虑上皮-间质转化特征和 TME 状态的重要性，我们重新审视它们在预测 FGFR3 突变 BLCA 中免疫检查点抑制剂反应中的相关性。本文强调了 FGFR 抑制剂 Erdafitinib 对 FGFR3 突变 BLCA 最初有希望但短暂的疗效，强调迫切需要解开耐药机制并确定未来组合研究的共同目标。对最近临床前和临床证据的全面分析揭示了耐药机制，包括二次突变、途径效应器的表观遗传改变、表型异质性以及 FGFR3 突变状态内的人群特异性变异。最后，我们讨论了组合治疗和合成致死等概念的潜力，以发现针对 FGFR3 突变 BLCA 的更有效的靶向疗法。© 2024 作者。约翰·威利出版的《癌症通讯》

In this review, we revisit the pivotal role of fibroblast growth factor receptor 3 (FGFR3) in bladder cancer (BLCA), underscoring its prevalence in both non-muscle-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 secondary mutations, 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.© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat‐sen University Cancer Center.