Vascular endothelial growth factor receptor 2 (VEGFR2), Hepatocyte growth factor receptor (MET), and AXL receptor tyrosine kinase (AXL) (VEGFR2/MET/AXL)

The VEGFR2/MET/AXL profile represents a synergistic group of receptor tyrosine kinases (RTKs) that are critical drivers of tumor progression, angiogenesis, and therapeutic resistance. Vascular Endothelial Growth Factor Receptor 2 (VEGFR2, also known as KDR) is the primary mediator of tumor-induced angiogenesis [1]. Hepatocyte Growth Factor Receptor (MET) and AXL are frequently upregulated as bypass mechanisms to escape anti-angiogenic therapy, promoting the epithelial-mesenchymal transition (EMT) and enhancing tumor invasiveness [2, 3]. Drugs targeting this specific combination, most notably cabozantinib, are designed to provide more durable clinical responses by blocking these compensatory escape pathways simultaneously [4]. In addition to these three primary targets, such multi-kinase inhibitors often affect other RTKs like RET, KIT, and FLT3, further contributing to their broad anti-tumor activity [4, 5]. This multi-targeted approach is particularly effective in advanced malignancies such as renal cell carcinoma and hepatocellular carcinoma, where co-activation of these receptors is a common feature of the disease landscape [4].

Other names

VEGFR2/MET/AXL multi-kinase profileMET/VEGFR2/AXL axisCabozantinib target profileKDR/MET/AXL

Simultaneous inhibition of the adenosine triphosphate (ATP) binding sites within the intracellular tyrosine kinase domains of VEGFR2, MET, and AXL, preventing autophosphorylation and downstream signaling through the PI3K/AKT, MAPK/ERK, and STAT3 pathways [4, 5].