Vascular endothelial growth factor receptor and fibroblast growth factor receptor family (VEGFR/FGFR)

The Vascular Endothelial Growth Factor Receptor (VEGFR) and Fibroblast Growth Factor Receptor (FGFR) families are distinct groups of receptor tyrosine kinases (RTKs) that are essential for vascular development and cellular homeostasis [UniProt]. The VEGFR family, including VEGFR1, VEGFR2, and VEGFR3, is the primary mediator of angiogenesis and lymphangiogenesis, responding to VEGF ligands to promote endothelial cell survival and migration [NIH StatPearls]. The FGFR family, comprising FGFR1 through FGFR4, regulates a broader array of processes, including embryonic development, wound healing, and cell differentiation through interactions with various fibroblast growth factors [PubMed: PMC4963171]. In oncology, both receptor families are frequently overexpressed or mutated, driving tumor neoangiogenesis and providing escape mechanisms for tumors under selective pressure [Nature Reviews Cancer, 2019]. Multi-kinase inhibitors like Lenvatinib and Nintedanib target the intracellular kinase domains of both families to achieve synergistic anti-tumor effects by simultaneously inhibiting vessel growth and direct tumor cell proliferation [PubChem]. However, the dual inhibition of these pathways is associated with specific toxicities, such as hypertension and proteinuria, reflecting the receptors' roles in maintaining normal vascular function [Journal of Clinical Oncology, 2020].

Other names

VEGFR/FGFR familyVEGF and FGF receptorsAngiogenic receptor tyrosine kinasesRTK Class IV and V

Competitive inhibition of the ATP-binding site within the intracellular tyrosine kinase domains of both VEGFR and FGFR, preventing autophosphorylation and downstream signaling through the RAS/MAPK and PI3K/AKT pathways.