Vascular endothelial growth factor receptor 1 (VEGFR1), Vascular endothelial growth factor receptor 2 (VEGFR2), and Vascular endothelial growth factor receptor 3 (VEGFR3) and multiple kinases (VEGFR1/2/3/MK)

The Vascular Endothelial Growth Factor Receptor (VEGFR) family, including VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), represents a group of receptor tyrosine kinases essential for the formation and maintenance of the vascular and lymphatic systems. These receptors are primarily expressed on endothelial cells and are activated by VEGF ligands to initiate signaling pathways like PI3K/Akt and PLC-gamma, which drive angiogenesis, vascular permeability, and cell survival (UniProt P17948, P35968). In the context of oncology, tumors often overexpress VEGF or its receptors to facilitate neoangiogenesis, providing the necessary blood supply for tumor expansion and metastatic spread (PubMed: 28345548). Therapeutic strategies often employ multi-kinase inhibitors (MKIs) that target the intracellular kinase domains of all three VEGFRs along with other kinases such as Platelet-derived growth factor receptor (PDGFR), KIT, and RAF to achieve broad anti-tumor and anti-angiogenic effects (StatPearls NBK542261). These inhibitors work by competing with ATP for the binding site within the kinase domain, effectively shutting down downstream signaling (PubMed: 28345548). While highly effective in treating various solid tumors like renal cell carcinoma and hepatocellular carcinoma, these inhibitors are associated with systemic side effects such as hypertension and hand-foot skin reactions due to the inhibition of these kinases in healthy tissues (PubMed: 30215169).

Other names

VEGFR familyVEGF receptorsMulti-kinase target profileReceptor tyrosine kinases (RTKs)Angiogenesis receptors

Inhibition of the intracellular tyrosine kinase domain of VEGFR1, VEGFR2, and VEGFR3, as well as other receptor tyrosine kinases (RTKs), by competing with ATP for the binding site, thereby blocking downstream signaling pathways involved in angiogenesis and tumor cell proliferation (StatPearls NBK542261).