Vascular endothelial growth factor and fibroblast growth factor receptor signaling complexes (VEGF/VEGFR and FGF/FGFR)

The VEGF/VEGFR and bFGF/FGFR signaling complexes are pivotal regulators of angiogenesis, the physiological process of new blood vessel formation. Vascular Endothelial Growth Factor (VEGF) and its receptors (VEGFR1-3) are the primary drivers of endothelial cell migration and tube formation (Ferrara, 2004, Endocrine Reviews). Basic Fibroblast Growth Factor (bFGF or FGF2) and its receptors (FGFR1-4) act synergistically with the VEGF pathway to promote vascular stability and endothelial cell proliferation (Presta et al., 2005, Cytokine & Growth Factor Reviews). In oncology, tumors often upregulate both pathways to sustain a robust blood supply, and the FGF pathway frequently serves as a bypass mechanism to develop resistance against VEGF-targeted monotherapies (Casanovas et al., 2005, Cancer Cell). Therapeutic agents targeting these complexes are typically multi-kinase inhibitors, such as Lenvatinib and Nintedanib, designed to simultaneously block both signaling axes to achieve more comprehensive anti-angiogenic effects (Matsui et al., 2011, Clinical Cancer Research). These complexes are also significant in ophthalmology, where their overactivation leads to neovascular diseases of the eye like age-related macular degeneration.

Other names

Angiogenic growth factor signaling pathwaysVEGF-FGF dual signalingPro-angiogenic receptor tyrosine kinase complexes

Inhibition of the intracellular tyrosine kinase domains of both VEGFR (1-3) and FGFR (1-4), which prevents receptor autophosphorylation and blocks downstream signaling pathways such as MAPK/ERK, PI3K/Akt, and PLC-gamma (Hilberg et al., 2008, Cancer Research; Matsui et al., 2011, Clinical Cancer Research).