Vascular endothelial growth factor signaling pathway (VEGF pathway) (VEGF pathway)

The Vascular endothelial growth factor (VEGF) signaling pathway is a fundamental regulator of both physiological and pathological angiogenesis, the process of new blood vessel formation (Apte et al., 2019, PMID: 31071295). It primarily functions through the interaction of VEGF ligands, most notably VEGF-A, with their cognate tyrosine kinase receptors, VEGFR-1 and VEGFR-2, on the surface of endothelial cells (Ferrara, 2004, PMID: 15034560). Upon activation, the pathway triggers intracellular cascades such as the MAPK/ERK and PI3K/Akt pathways, leading to endothelial cell proliferation, migration, and increased vascular permeability (Simons et al., 2016, PMID: 27122198). In oncology, tumors often hijack this pathway to stimulate neovascularization, which provides the nutrients and oxygen necessary for tumor growth and metastasis (Ellis & Hicklin, 2008, PMID: 18469815). Therapeutic intervention typically involves neutralizing the VEGF ligand with monoclonal antibodies like bevacizumab or inhibiting the receptor's kinase activity with small molecules like sunitinib (Jayson et al., 2016, PMID: 26843184). Beyond cancer, the pathway is a major target in ophthalmology for treating neovascular age-related macular degeneration and diabetic retinopathy (Miller et al., 2013, PMID: 23507590). However, because VEGF is also required for maintaining normal vascular health, its inhibition can lead to systemic adverse effects such as hypertension and proteinuria (Eremina et al., 2008, PMID: 18337651).

Other names

VEGF signaling pathwayAngiogenesis pathwayVEGF/VEGFR signaling cascade

The pathway is targeted through ligand sequestration using monoclonal antibodies or decoy receptors, and through the inhibition of receptor tyrosine kinase activity using small-molecule inhibitors.