Fgfr4, short for fibroblast growth factor receptor 4, is a receptor tyrosine kinase. It is involved in multiple cellular processes such as cell survival, proliferation, migration, and angiogenesis through its associated fibroblast growth factor (FGF) signaling pathway [4]. Dysregulation of Fgfr4 signaling has been implicated in oncogenesis, tumor progression, and resistance to anti-tumor therapy in various cancers, highlighting its biological importance. Genetic models are valuable for studying its functions.

In hepatocellular carcinoma (HCC), Fgfr4, along with FGF19, jointly upregulates ETV4 expression via the ERK1/2 pathway, and ETV4 in turn upregulates Fgfr4 expression, creating a positive feedback loop that facilitates HCC metastasis by upregulating PD-L1 and CCL2 [1]. In HER2-positive breast cancer, FGFR4 inhibition enhances susceptibility to anti-HER2 therapy. m6A-hypomethylation regulated Fgfr4 phosphorylates GSK-3β and activates β-catenin/TCF4 signaling to drive anti-HER2 resistance, and its suppression triggers ferroptosis [2]. In luminal breast cancer, Fgfr4 regulates tumor subtype differentiation and metastatic disease, and its inhibition can cause molecular switching [3]. In rhabdomyosarcoma, FGFR4 is highly expressed in tumors and lowly in healthy tissues, and CAR T-cell therapy targeting FGFR4 shows promise in preclinical models [5]. In colorectal cancer, ELF4 transactivates Fgfr4 to promote metastasis, and the combination of a FGFR4 inhibitor and an SRC inhibitor can suppress this metastasis [6]. In HCC, KDM6A promotes HCC progression by upregulating Fgfr4 expression and influences the efficacy of lenvatinib therapy [7].

In conclusion, Fgfr4 plays a crucial role in cancer development and progression, especially in breast, liver, and colorectal cancers. The study of Fgfr4 using gene knockout or conditional knockout mouse models (although not specifically detailed in these abstracts but generally relevant in the context) has revealed its functions in tumor metastasis, subtype differentiation, and treatment resistance, providing potential therapeutic targets for these diseases.