Department of Oral Biology, Augusta University, Augusta, GA 30912, United States.
Department of Biology, Presbyterian College, Clinton, SC 29325, United States.
Curr Cancer Drug Targets. 2019;19(1):17-25. doi: 10.2174/1568009618666180319091731.
Coordination between the amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme β-klotho has been found to play pivotal roles in mediating tumor development and progression. Aberrant FGF19-FGFR4 signaling has been implicated in driving specific tumorigenic events including cancer cell proliferation, apoptosis resistance, and metastasis by activating a myriad of downstream signaling cascades. As an attractive target, several strategies implemented to disrupt the FGF19-FGFR4 axis have been developed in recent years, and FGF19-FGFR4 binding inhibitors are being intensely evaluated for their clinical use in treating FGF19-FGFR4 implicated cancers. Based on the established work, this review aims to detail how the FGF19-FGFR4 signaling pathway plays a vital role in cancer progression and why disrupting communication between FGF19 and FGFR4 serves as a promising therapeutic strategy for disrupting cancer progression.
已发现成纤维细胞生长因子 FGF19 的扩增、其相应受体 FGFR4 的过表达以及下游跨膜酶β-klotho 的过度激活之间的协调在介导肿瘤发生和进展中起着关键作用。异常的 FGF19-FGFR4 信号转导已被证明通过激活无数下游信号级联来驱动包括癌细胞增殖、凋亡抵抗和转移在内的特定致癌事件。作为一个有吸引力的靶点，近年来已经实施了几种破坏 FGF19-FGFR4 轴的策略，并且正在强烈评估 FGF19-FGFR4 结合抑制剂在治疗涉及 FGF19-FGFR4 的癌症中的临床用途。基于已建立的工作，本综述旨在详细说明 FGF19-FGFR4 信号通路如何在癌症进展中发挥重要作用，以及为什么破坏 FGF19 和 FGFR4 之间的通信是破坏癌症进展的有前途的治疗策略。
