Fibroblast growth factor receptor 2 and 3 (FGFR2 and FGFR3)

Fibroblast growth factor receptor 2 (FGFR2) and fibroblast growth factor receptor 3 (FGFR3) are closely related receptor tyrosine kinases that belong to the FGFR family, consisting of four main members. Both receptors are transmembrane proteins characterized by three extracellular immunoglobulin-like domains, a single membrane-spanning segment, and a cytoplasmic tyrosine kinase domain[5][1][8]. They function by binding to fibroblast growth factors (FGFs), leading to receptor dimerization and activation of intracellular kinase activity, which triggers downstream signaling pathways controlling cell proliferation, differentiation, survival, angiogenesis, and tissue development[3][9]. Alternative splicing creates multiple receptor isoforms with distinct ligand affinities and tissue distributions[4]. Mutations, gene amplifications, or chromosomal rearrangements in FGFR2 or FGFR3 drive oncogenic signaling in various cancers (e.g., cholangiocarcinoma, urothelial carcinoma, glioblastoma), and also cause hereditary skeletal dysplasias and craniosynostosis syndromes[6][3][5]. Multiple targeted therapies (especially tyrosine kinase inhibitors) have been developed to block aberrant FGFR2 and FGFR3 signaling in cancer, and biomarker-driven patient selection is increasingly common. Major safety concerns with inhibitors reflect the physiological roles of FGFRs in phosphate homeostasis, bone growth, and tissue maintenance.

Other names

FGFR2: CD332FGFR3: CD333Fibroblast growth factor receptor-2Fibroblast growth factor receptor-3FGFR-2FGFR-3

Inhibition of tyrosine kinase activity, leading to blockade of downstream mitogenic and survival signaling pathways (e.g., RAS/MAPK, PI3K/AKT, PLCγ). This involves inhibition of FGF ligand binding and receptor dimerization or activation, ultimately inducing cancer cell death or cell cycle arrest via signal disruption.