Fibroblast growth factor receptor 1-3 (FGFR1-3) (FGFR1-3)

Fibroblast growth factor receptors 1, 2, and 3 (FGFR1-3) are a subgroup of the FGFR family of receptor tyrosine kinases that mediate essential cellular signals for growth and development (UniProt, 2024). These receptors are activated by the binding of fibroblast growth factor (FGF) ligands, which triggers receptor dimerization and the activation of their intracellular kinase domains through trans-autophosphorylation (PubMed, 2017). This process initiates several critical downstream signaling pathways, including the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, which regulate cell proliferation, survival, and differentiation (NIH, 2023). In various malignancies, FGFR1-3 are frequently altered via gene amplification, point mutations, or chromosomal translocations, leading to aberrant, constitutive signaling that promotes tumor growth and survival (Nature Reviews Cancer, 2017). Therapeutic strategies targeting these receptors primarily involve small-molecule tyrosine kinase inhibitors that compete with ATP for binding to the kinase domain, thereby blocking downstream signaling (PubMed, 2021). While these inhibitors have shown significant clinical efficacy in cancers such as urothelial carcinoma and cholangiocarcinoma, they are also associated with unique toxicities, most notably hyperphosphatemia, which results from the inhibition of FGFR1-mediated phosphate regulation in the kidney (ASCO, 2025).

Other names

FGFR1FGFR2FGFR3CD331CD332CD333Basic fibroblast growth factor receptor 1Keratinocyte growth factor receptorFGFR1-3 kinasesFms-related tyrosine kinase 2BEKACH

ATP-competitive inhibition of the intracellular tyrosine kinase domain of FGFR1, FGFR2, and FGFR3, preventing receptor autophosphorylation and downstream signaling (PubMed, 2021).