Vascular endothelial growth factor and fibroblast growth factor receptor pathways (VEGF/FGF pathways)

The Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) pathways are essential mediators of angiogenesis and vascular maintenance (Ferrara & Adamis, 2016 [1]). On endothelial cells, VEGF primarily signals through VEGFR2 to stimulate proliferation and permeability, while FGF signaling via FGFRs promotes cell survival and migration, often acting as a compensatory mechanism when VEGF signaling is blocked (Turner & Grose, 2010 [2]; Casanovas et al., 2005 [3]). These pathways are frequently co-opted by tumors to facilitate neovascularization, which is necessary for tumor growth and hematogenous spread (Goel & Mercurio, 2013 [4]). Drugs targeting these components, such as the multi-kinase inhibitors Lenvatinib and Nintedanib, aim to disrupt the blood supply to tumors by inhibiting the intracellular tyrosine kinase domains of both VEGFR and FGFR (Hilberg et al., 2008 [5]). Beyond oncology, the VEGF pathway is a primary target in treating neovascular ocular diseases like age-related macular degeneration (AMD) (Miller et al., 2013 [6]).

Other names

VEGF-FGF signaling axisAngiogenic growth factor pathwaysVEGFR and FGFR signalingPro-angiogenic receptor tyrosine kinases

Simultaneous inhibition of the intracellular tyrosine kinase domains of vascular endothelial growth factor receptors (VEGFR1, VEGFR2, VEGFR3) and fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3, FGFR4), which prevents the activation of downstream signaling pathways like MAPK/ERK and PI3K/Akt, thereby inhibiting endothelial cell proliferation, migration, and tube formation (Hilberg et al., 2008 [5]; Matsui et al., 2008 [7]).