Vascular endothelial growth factor (VEGF) (VEGF)

The Vascular Endothelial Growth Factor (VEGF) family consists of several related glycoproteins, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and Placental Growth Factor (PlGF), which act as master regulators of angiogenesis and lymphangiogenesis (UniProt P15692; NCBI Gene ID: 7422). These ligands function by binding to specific cell-surface receptor tyrosine kinases (VEGFR-1, VEGFR-2, and VEGFR-3), triggering signaling cascades that promote endothelial cell proliferation, migration, and survival (StatPearls: VEGF Inhibitors). VEGF-A is the most potent inducer of vascular permeability and angiogenesis, playing a central role in both normal physiological processes like wound healing and pathological conditions such as tumor growth and neovascular eye diseases (PubMed: PMID 15660110). In oncology, tumors overexpress VEGF to stimulate the formation of new blood vessels, a process known as the "angiogenic switch," which provides the nutrients and oxygen necessary for tumor expansion and metastasis (NIH: Cancer.gov). Therapeutic agents targeting these ligands include monoclonal antibodies like bevacizumab and "trap" fusion proteins like aflibercept, which sequester multiple VEGF family members to prevent receptor activation (FDA: Zaltrap Label). While highly effective, these therapies are associated with specific class-effect toxicities, including hypertension, proteinuria, and impaired wound healing, due to the systemic inhibition of physiological vascular maintenance (Journal of Clinical Oncology: DOI 10.1200/JCO.2008.16.3956).

Other names

Vascular permeability factorVPFVEGF familyVEGF-AVEGF-BVEGF-CVEGF-DPlacental growth factorPlGF

These drugs function as neutralizing agents that bind to and sequester VEGF ligands (such as VEGF-A, VEGF-B, and PlGF) in the extracellular space. By preventing these ligands from interacting with their cognate receptors (VEGFR-1 and VEGFR-2), the drugs inhibit the activation of downstream signaling pathways, including the MAPK and PI3K/Akt pathways, which are essential for endothelial cell proliferation, survival, and vascular permeability.