The FGFR signaling pathway is integral to cellular activities, including proliferation, differentiation, and survival. Dysregulation of this pathway is implicated in numerous human cancers, positioning FGFR as a prominent therapeutic target. Here, we conduct a comprehensive review of the function, signaling pathways and abnormal alterations of FGFR, as well as its role in tumorigenesis and development. Additionally, we provide an in-depth analysis of pivotal phase 2 and 3 clinical trials evaluating the performance and safety of FGFR inhibitors in oncology, thereby shedding light on the current state of clinical research in this field. Then, we highlight four drugs that have been approved for marketing by the FDA, offering insights into their molecular mechanisms and clinical achievements. Our discussion encompasses the intricate landscape of FGFR-driven tumorigenesis, current techniques for pinpointing FGFR anomalies, and clinical experiences with FGFR inhibitor regimens. Furthermore, we discuss the inherent challenges of targeting the FGFR pathway, encompassing resistance mechanisms such as activation by gatekeeper mutations, alternative pathways, and potential adverse reactions. By synthesizing the current evidence, we underscore the potential of FGFR-centric therapies to enhance patient prognosis, while emphasizing the imperative need for continued research to surmount resistance and optimize treatment modalities.

中文翻译：

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靶向 FGFR 进行癌症治疗


FGFR 信号转导通路是细胞活动（包括增殖、分化和存活）不可或缺的一部分。该通路的失调与许多人类癌症有关，使 FGFR 成为重要的治疗靶点。在这里，我们对 FGFR 的功能、信号通路和异常改变，以及它在肿瘤发生和发展中的作用进行了全面综述。此外，我们还对评估 FGFR 抑制剂在肿瘤学中的性能和安全性的关键 2 期和 3 期临床试验进行了深入分析，从而阐明了该领域临床研究的现状。然后，我们重点介绍了四种已被 FDA 批准上市的药物，提供了对其分子机制和临床成就的见解。我们的讨论包括 FGFR 驱动的肿瘤发生的复杂情况、当前确定 FGFR 异常的技术以及 FGFR 抑制剂方案的临床经验。此外，我们讨论了靶向 FGFR 通路的固有挑战，包括耐药机制，例如守门人突变激活、替代通路和潜在的不良反应。通过综合当前证据，我们强调了以 FGFR 为中心的疗法在改善患者预后方面的潜力，同时强调迫切需要继续研究以克服耐药性并优化治疗方式。