Vascular endothelial growth factor receptor 2, Vascular endothelial growth factor receptor 3 (VEGFR2, VEGFR3)

Vascular endothelial growth factor receptor 2 (VEGFR2) and vascular endothelial growth factor receptor 3 (VEGFR3) are transmembrane receptor tyrosine kinases primarily expressed on endothelial cells. VEGFR2 is the principal mediator of angiogenesis, controlling endothelial cell proliferation, migration, survival, and vascular permeability in response to VEGF-A, and is critical for vascular development and neovascularization in both physiological and pathological conditions such as cancer and eye disease[3][5][7][8]. VEGFR3 primarily regulates lymphangiogenesis via binding to VEGF-C and VEGF-D, and is essential for lymphatic vascular development and function[1][4][7]. Both receptors have a similar modular structure with seven extracellular immunoglobulin-like domains, a single transmembrane domain, and a split intracellular tyrosine kinase domain[1][3][5]. They are established therapeutic targets in oncology and vascular-related diseases, with multiple approved drugs targeting one or both receptors via antibody and small molecule mechanisms[3][5][6]. Major therapeutic challenges include management of side effects such as hypertension and edema, and resistance mechanisms arising during long-term therapy[5][7].

Other names

VEGFR2: Kinase insert domain receptor (KDR)VEGFR2: Fetal liver kinase 1 (Flk-1)VEGFR3: Fms-like tyrosine kinase 4 (FLT4)

Inhibition of VEGF ligand binding (antibodies or ligand traps); Inhibition of receptor tyrosine kinase activity (small molecule tyrosine kinase inhibitors); Disruption of downstream signaling pathways leading to blockade of angiogenesis and/or lymphangiogenesis, endothelial cell proliferation, migration, and survival[3][5][6]