Interrupting the FGF19-FGFR4 Axis to Therapeutically Disrupt Cancer Progression

Coordination between the amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme beta-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.