FGFR信号通路在肿瘤中的作用机制与靶向治疗研究进展

Research progress on the mechanism of FGFR signaling pathway in tumors and targeted therapy

摘要

成纤维细胞生长因子（fibroblast growth factor，FGF）及成纤维细胞生长因子受体（fibroblast growth factor receptor，FGFR）信号通路是调控细胞增殖、分化、迁移和存活的关键分子枢纽，在胚胎发育、组织修复和代谢稳态等多种生理过程中扮演着核心角色。该通路的异常激活，特别是由FGFR家族基因（FGFR1~4）的突变、扩增或染色体重排等基因异常所驱动，已成为多种恶性肿瘤发生与发展的重要致癌因素。携带这类变异的患者总体生存预后较差。近年来随着精准医疗理念的深入和高通量测序技术的普及，针对FGFR变异的新药研发不断取得进展，已有多种小分子抑制剂获批用于治疗携带特定FGFR基因异常的肿瘤患者，显著改善了这类患者的预后。文章旨在探讨肿瘤患者中FGFR信号通路与肿瘤发生发展的相关性及存在FGFR信号通路变异的肿瘤患者的治疗方案，着重探讨了FGFR靶向治疗新进展。

Abstract

Fibroblast growth factor（FGF）and fibroblast growth factor receptor（FGFR）signaling pathways are key molecular hubs that regulate cell proliferation，differentiation，migration，and survival. They play a central role in various physiological processes such as embryonic development，tissue repair，and metabolic homeostasis. Abnormal activation of this pathway，driven by genetic abnormalities such as mutations，amplification，or chromosomal rearrangements in FGFR family genes（FGFR1-4），has become an important oncogenic factor in the development of various malignant tumors. Patients carrying such variations generally have a poorer overall survival prognosis. In recent years，with the deepening of the concept of precision medicine and the popularization of high-throughput sequencing technology，new drug development targeting FGFR variations has made continuous progress. Various small molecule inhibitors have been approved for the treatment of tumor patients with specific FGFR gene abnormalities，significantly improving the prognosis of these patients. This article aims to explore the correlation between the FGFR signaling pathway and tumor occurrence and development in tumor patients，as well as the treatment options for tumor patients with FGFR signaling pathway variations，and focuses on the new progress in FGFR-targeted therapy.

关键词

成纤维细胞生长因子受体 / 肿瘤 / 靶向治疗

Key words

fibroblast growth factor receptor / tumor / targeted therapy

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基金资助

国家自然科学基金青年基金(81902327)

江苏省科技厅基础研究计划（自然科学基金）(BK20191064)