Fibroblast growth factor receptor (FGFR)

Fibroblast growth factor receptors (FGFRs) are a family of four transmembrane receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, and FGFR4) that play essential roles in cell proliferation, differentiation, and survival (UniProt, 2024). These receptors are activated by the binding of fibroblast growth factor (FGF) ligands, which triggers dimerization and the activation of intracellular signaling cascades such as the RAS-MAPK and PI3K-AKT pathways (StatPearls, 2023). Genetic alterations in FGFRs, including gene amplifications, point mutations, and chromosomal fusions, are frequently observed in various cancers, such as urothelial carcinoma, cholangiocarcinoma, and breast cancer (Nature Reviews Clinical Oncology, 2021). Consequently, FGFRs have emerged as significant therapeutic targets, leading to the development of selective tyrosine kinase inhibitors like erdafitinib and pemigatinib (FDA, 2020). Beyond oncology, FGFR signaling is vital for normal embryonic development and bone growth, and mutations in these receptors are associated with skeletal dysplasias like achondroplasia (PubMed, 2022). Clinical use of FGFR inhibitors is often limited by specific toxicities, most notably hyperphosphatemia, which occurs due to the inhibition of FGF23 signaling in the renal proximal tubules (Journal of Hematology & Oncology, 2022).

Other names

FGFR familyCD331CD332CD333CD334FGFR1FGFR2FGFR3FGFR4Tyrosine-protein kinase receptor

ATP-competitive inhibition of the intracellular tyrosine kinase domain, preventing receptor autophosphorylation and the subsequent activation of downstream signaling pathways like MAPK and PI3K (Nature Reviews Drug Discovery, 2019).