Vascular endothelial growth factor receptor signaling pathway (VEGFR signaling pathway)

The vascular endothelial growth factor receptor signaling pathway comprises a network of ligand-receptor interactions primarily involving VEGF-A, VEGF-B, VEGF-C, and VEGF-D ligands and the VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4) receptors[2][7][8]. Upon ligand binding, VEGFRs dimerize and activate intrinsic tyrosine kinase domains, triggering downstream signaling pathways such as PI3K/AKT/mTOR, MAPK/ERK, and PLCγ that drive endothelial cell proliferation, migration, survival, vascular permeability, and the formation of new blood and lymphatic vessels[2][7][8]. Dysregulation leads to pathological angiogenesis implicated in cancer progression, ocular neovascular diseases, and inflammatory conditions[7]. Pharmacologic blockade of the VEGFR pathway includes monoclonal antibodies targeting VEGF (e.g., bevacizumab) and small-molecule inhibitors of VEGFR kinases (e.g., sorafenib), which are approved for various malignancies and eye diseases[5][7]. Key therapeutic challenges include resistance, adverse vascular events, and balancing anti-angiogenic efficacy with normal tissue vascular function[7].

Other names

VEGF receptor pathwayVEGF-VEGFR pathwayVEGF signalingVEGFR axis

Inhibition of VEGF ligand binding to VEGFRs, Inhibition of VEGFR tyrosine kinase activity, Neutralization of VEGF ligands, Blockade of downstream angiogenic signaling