FGF19在恶性肿瘤中的潜在临床价值及相关药物进展

The potential clinical value of FGF19 in malignant tumors and recent progress of related drugs

成纤维细胞生长因子(FGF)19是一种重要的激素样成纤维细胞生长因子,发挥调节细胞生理功能及代谢等作用。研究显示,在恶性肿瘤的发生和发展中FGF19扮演着重要角色。FGF19/成纤维细胞生长因子受体(FGFR)4信号激活与癌症的发生和进展密切相关,是具潜力的抗肿瘤治疗靶点。靶向药物是抗肿瘤治疗的重要手段,靶向FGF19/FGFR4已成为近期的研究热点。靶向FGF19/FGFR4的策略大致分为两大类:靶向FGF19的治疗策略和靶向FGFR4的治疗策略。针对FGFR4的药物涵盖泛FGFR抑制剂、FGFR4特异性小分子抑制剂以及FGFR4特异性单克隆抗体等。FGFR4抑制剂的开发和设计等研究已取得重大进展,但仍面临诸多挑战。本文对FGF19的生理学功能、FGF19与肿瘤发生发展的关系、国内外相关研究进展以及FGF19相关药物进行详细综述,以期为基础科研及临床诊疗提供一定参考。

Fibroblast growth factor(FGF)19 is an important hormone-like fibroblast growth factor that regulates various physiological and metabolic processes.Studies have suggested that as a driving factor of a variety of malignant tumors,FGF19 plays an important role in the occurrence and development of malignant tumors.The activation of FGF19/fibroblast growth factor receptor(FGFR)4 signal is closely related to the recurrence and progression of cancer,suggesting that FGF19/FGFR4 is a potential anti-cancer therapeutic target.Targeting FGF19/FGFR4 provides a novel anti-tumor treatment strategy.Nowadays,the research on FGF and FGFR has become a new hot spot around world.Strategies targeting FGF19/FGFR4 are generally divided into two categories:therapeutic strategies targeting FGF19 and therapeutic strategies targeting FGFR4.Therapeutic strategies targeting FGFR4 include pan-FGFR inhibitors,FGFR4-specific small molecule inhibitors,and FGFR4-specific monoclonal antibodies.Significant progress has been made in the development of selective FGFR4 inhibitors,but there are still many future challenges.This article provides a detailed review of the physiological functions of FGF19,the relationship between FGF19 and the occurence and development of tumors,FGF19-related research progress,and FGF19/FGFR4 related drugs.The purpose of this review is to provide a certain reference for basic scientific research and clinical diagnosis and treatment.