Fibroblast growth factor receptor 1 (FGFR1); Fibroblast growth factor receptor 2 (FGFR2) (FGFR1; FGFR2)

Fibroblast growth factor receptor 1 and 2 are cell surface receptor tyrosine kinases, each consisting of an extracellular ligand-binding domain with three immunoglobulin-like loops, a single transmembrane helix, and an intracellular split kinase domain. They bind to multiple fibroblast growth factors (FGFs), initiating dimerization and autophosphorylation that activate several downstream signaling pathways (notably RAS-MAPK, PI3K-AKT, and PLCγ) vital for cell proliferation, survival, differentiation, and tissue repair. Aberrant activation, such as through gene amplification, fusion, or activating mutation, is implicated in numerous human cancers and developmental disorders. Therapeutically, selective inhibition of FGFR1/FGFR2 is employed in cancers driven by these aberrations, but physiological roles in phosphate metabolism and tissue homeostasis present safety challenges.

Other names

FGFR1: FLGFGFR1: bFGF receptorFGFR2: BEKAdditional: FGF receptor 1Additional: FGF receptor 2

Small molecule inhibitors block ATP binding to the tyrosine kinase domain, inhibiting phosphorylation and downstream signaling. Monoclonal antibodies and ligand traps can inhibit ligand-receptor interaction (less common clinically). Drug-induced degradation (some small molecules and PROTACs under investigation).