Vascular endothelial growth factor receptor, Fibroblast growth factor receptor, Platelet-derived growth factor receptor alpha, RET proto-oncogene, and KIT proto-oncogene receptor tyrosine kinase (VEGFR, FGFR, PDGFRα, RET, KIT)

This target profile consists of a group of Receptor Tyrosine Kinases (RTKs) that are central to tumor growth, angiogenesis, and lymphangiogenesis [1, 2, 6]. The group includes Vascular Endothelial Growth Factor Receptors (VEGFR1-3), Fibroblast Growth Factor Receptors (FGFR1-4), Platelet-Derived Growth Factor Receptor alpha (PDGFRα), and the proto-oncogenes RET and KIT [1, 2, 3, 4, 5]. These receptors normally regulate essential cellular processes such as proliferation, migration, and survival; however, their dysregulation is a hallmark of many cancers [6]. Multi-kinase inhibitors (MKIs) like lenvatinib are designed to target this specific combination of kinases to simultaneously disrupt the tumor's blood supply and its internal growth signaling [6]. By binding to the ATP-binding pocket of these kinases, these drugs inhibit downstream cascades like the RAS/MAPK and PI3K/AKT pathways, leading to reduced tumor vascularization and increased apoptosis [6, 7]. While effective in treating various solid tumors, the broad-spectrum activity of targeting these multiple receptors often results in characteristic toxicities such as hypertension and hand-foot syndrome [6].

Other names

Multi-kinase target profileLenvatinib target clusterRTK group

Inhibition of the intracellular tyrosine kinase domains of multiple receptors, blocking ATP binding and preventing downstream signaling through the MAPK/ERK and PI3K/AKT pathways [6, 7].