Vascular endothelial growth factor receptor (VEGFR) and RAF kinase (VEGFR/RAF)

Vascular endothelial growth factor receptors (VEGFR) and RAF kinases are distinct but interconnected signaling proteins that play pivotal roles in tumor growth and progression. VEGFRs are receptor tyrosine kinases located on the surface of endothelial cells that, upon activation by VEGF ligands, trigger angiogenesis to supply the tumor with blood [1]. RAF kinases, including A-RAF, B-RAF, and C-RAF, are intracellular serine/threonine kinases that act as key mediators in the RAS-RAF-MEK-ERK signaling cascade, which promotes cell division and survival [2]. In many malignancies, these pathways are overactive due to mutations or ligand overexpression, making them prime therapeutic targets. Multi-kinase inhibitors like sorafenib and regorafenib are designed to hit both VEGFR and RAF, providing a dual-pronged attack that inhibits both the tumor's vascular support and its internal proliferative signaling [3, 4]. This combined inhibition is particularly effective in treating solid tumors such as renal cell carcinoma and hepatocellular carcinoma, though it is often associated with systemic toxicities like hypertension and dermatologic reactions [5]. Sources: [1] UniProt P35968 (VEGFR2); [2] UniProt P15056 (BRAF); [3] PubChem CID 133021 (Sorafenib); [4] DrugBank DB08896 (Regorafenib); [5] PubMed PMID 28456709.

Other names

VEGF receptorRAF proto-oncogene serine/threonine-protein kinaseKDRFLT1FLT4BRAFCRAFRaf-1VEGFR/RAF dual target

Multi-kinase inhibition involving the competitive blockade of ATP-binding sites on both Vascular Endothelial Growth Factor Receptors (VEGFR-1, -2, -3) and RAF kinases (A-RAF, B-RAF, and C-RAF) [4, 5].