Fibroblast growth factor receptor 3 (FGFR3) (G697C mutation) (FGFR3 G697C)

Fibroblast growth factor receptor 3 (FGFR3) is a transmembrane receptor tyrosine kinase that regulates essential cellular processes including proliferation, differentiation, and apoptosis (UniProt P22607). The G697C mutation is a somatic point mutation located within the highly conserved tyrosine kinase domain of the receptor (MyCancerGenome). This specific alteration leads to the constitutive, ligand-independent activation of the receptor, driving downstream signaling through the MAPK and PI3K/AKT pathways (PubMed: 24121495). FGFR3 G697C is primarily associated with oncogenesis, particularly in urothelial carcinomas and certain lung adenocarcinomas (NIH: Genetics Home Reference). Therapeutic intervention for this target involves the use of selective FGFR inhibitors, such as erdafitinib, which are designed to bind to the ATP-binding pocket of the kinase domain (FDA: Balversa Label). These inhibitors effectively suppress the overactive signaling that promotes tumor growth in patients carrying the G697C mutation. Clinical use of these drugs requires monitoring for specific adverse effects, most notably hyperphosphatemia caused by the inhibition of FGF23 signaling in the kidneys. Additionally, ocular toxicities like central serous retinopathy are significant safety concerns associated with targeting this receptor (PubMed: 31461644).

Other names

FGFR3CD333ACHCEK2JTK4Fibroblast growth factor receptor 3 G697C

Small-molecule inhibition of the FGFR3 tyrosine kinase domain by ATP-competitive binding, preventing autophosphorylation and subsequent activation of downstream oncogenic pathways like MAPK/ERK.