FGFR4 (fibroblast growth factor receptor 4) is a tyrosine kinase receptor that plays critical roles in cancer progression and therapeutic resistance. The receptor functions through multiple signaling pathways, including ERK1/2 and β-catenin/TCF4 signaling cascades 12. FGFR4 promotes tumor metastasis through various mechanisms: it facilitates hepatocellular carcinoma metastasis by upregulating ETV4, which increases PD-L1 and CCL2 expression, leading to immunosuppressive tumor microenvironments 1. In breast cancer, FGFR4 drives anti-HER2 resistance by preventing ferroptotic cell death through regulation of glutathione synthesis and iron homeostasis via the β-catenin/SLC7A11/FPN1 axis 2. The receptor also promotes cancer-associated fibroblast (CAF) activation in colon cancer through CXCL10-CXCR3 axis signaling 3. Clinically, FGFR4 expression correlates with poor prognosis and advanced cancer stages across multiple tumor types 45. FGFR4 inhibition shows therapeutic promise, with inhibitors like futibatinib demonstrating selective antitumor activity 6, and combination therapies targeting FGFR4 alongside immune checkpoint inhibitors showing enhanced efficacy 7. The receptor is also being explored as a target for CAR T-cell therapies in rhabdomyosarcoma 8.