Vascular endothelial growth factor receptor family (VEGFR family) (VEGFR family)

Class V receptor tyrosine kinases, primarily known as the vascular endothelial growth factor receptor (VEGFR) family, are essential mediators of blood and lymphatic vessel development (Lemmon & Schlessinger, 2010). This family consists of three primary members: VEGFR1 (Flt-1), VEGFR2 (KDR/Flk-1), and VEGFR3 (Flt-4), each characterized by seven extracellular immunoglobulin-like domains and an intracellular tyrosine kinase domain (UniProt Consortium, 2024). These receptors are activated by the binding of VEGF ligands, which triggers dimerization and autophosphorylation, leading to the activation of downstream pathways such as MAPK/ERK and PI3K/Akt (Simons et al., 2016). VEGFR2 is the principal driver of angiogenesis and vascular permeability, while VEGFR3 is the master regulator of lymphangiogenesis. In oncology, the overexpression or overactivation of Class V RTKs is a hallmark of tumor progression, as it facilitates the neovascularization required for tumor growth and metastatic spread (StatPearls, 2023). Therapeutic strategies targeting this family include small-molecule tyrosine kinase inhibitors (TKIs) like sunitinib and pazopanib, as well as monoclonal antibodies like ramucirumab that block ligand-receptor interactions. These agents are standard of care for various solid tumors, including renal cell carcinoma and hepatocellular carcinoma, but are associated with distinct toxicities such as hypertension and proteinuria.

Other names

Class V receptor tyrosine kinaseVEGF receptorsVEGFRsFlt familyVascular endothelial growth factor receptors

Drugs targeting Class V receptor tyrosine kinases act by either competitively inhibiting the ATP-binding site of the intracellular kinase domain (small-molecule TKIs) or by binding to the extracellular domain of the receptor to prevent ligand-induced activation (monoclonal antibodies), thereby suppressing downstream pro-angiogenic and proliferative signaling pathways.