Targeting FGFR for cancer therapy

Abstract

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.