Fibroblast growth factor receptor (FGFR) (FGFR)

Fibroblast growth factor receptors (FGFRs) are a family of four transmembrane receptor tyrosine kinases (FGFR1-4) that are activated by the binding of fibroblast growth factors, including FGF-2 (basic FGF). This interaction, facilitated by heparin sulfate proteoglycans, induces receptor dimerization and the phosphorylation of intracellular tyrosine residues, which serves as a docking site for adapter proteins to trigger signaling cascades like RAS-MAPK and PI3K-AKT (Source: UniProt, PubMed). These receptors are vital for physiological processes such as embryonic development, angiogenesis, and wound healing (Source: NIH). However, aberrant FGFR signaling—driven by gene amplifications, mutations, or fusions—is implicated in the pathogenesis of several cancers, including bladder cancer and cholangiocarcinoma (Source: Nature Reviews Cancer). Therapeutic strategies targeting these receptors primarily involve small-molecule tyrosine kinase inhibitors (TKIs) that block the ATP-binding site, effectively halting tumor growth and survival (Source: FDA). Despite their efficacy, FGFR inhibitors are associated with unique class-effect toxicities, most notably hyperphosphatemia due to the inhibition of FGF23 signaling, as well as dermatological and ocular adverse events (Source: StatPearls).

Other names

FGFR1FGFR2FGFR3FGFR4CD331CD332CD333CD334Basic fibroblast growth factor receptorFGF-2 receptorHeparin-binding growth factor receptorFGF receptor

Competitive inhibition of the ATP-binding site within the intracellular tyrosine kinase domain of the receptor, which prevents autophosphorylation and subsequent activation of downstream oncogenic signaling pathways such as RAS-MAPK, PI3K-AKT, and PLCγ (Source: PubMed, NIH).