Fibroblast growth factor receptor 2 (FGFR2) (FGFR2)

Fibroblast growth factor receptor 2 (FGFR2) is a transmembrane receptor tyrosine kinase that plays a fundamental role in human development and tissue homeostasis [1, 5, 11]. It consists of an extracellular ligand-binding domain, a single-pass transmembrane segment, and an intracellular tyrosine kinase domain that triggers downstream signaling cascades such as the MAPK and PI3K-AKT pathways upon activation [2, 11, 14]. FGFR2 is essential for embryonic development, particularly in the formation of the skeletal system, and regulates processes like cell proliferation, differentiation, and angiogenesis [5, 18, 22]. In clinical oncology, FGFR2 is a well-validated therapeutic target due to its frequent dysregulation via gene fusions, amplifications, and activating mutations in cancers such as intrahepatic cholangiocarcinoma and gastric cancer [2, 3, 16, 18]. Therapeutic interventions include selective small-molecule inhibitors that target the kinase domain and monoclonal antibodies that block extracellular ligand interactions [3, 8, 17]. Despite the success of these targeted therapies, clinical management is often complicated by the emergence of resistance mutations and specific adverse effects, most notably hyperphosphatemia resulting from the inhibition of FGF23 signaling [2, 3, 14, 16].

Other names

CD332 [1]BEK [1]BFR-1 [1]CEK3 [1]CFD1 [1]ECT1 [1]JWS [1]K-SAM [1]KGFR [1]TK14 [1]TK25 [1]

Inhibition of the intracellular tyrosine kinase domain by competitive binding to the ATP-binding pocket [3, 8, 14], or extracellular blockade of ligand binding and receptor dimerization using monoclonal antibodies [3, 17].