Cabozantinib-sensitive tyrosine kinases

Cabozantinib-sensitive tyrosine kinases are a specific cluster of receptor tyrosine kinases (RTKs) that are potently inhibited by the small-molecule drug cabozantinib. The primary members of this group include MET (Hepatocyte growth factor receptor), VEGFR2 (Vascular endothelial growth factor receptor 2), and AXL, alongside others such as RET, KIT, and FLT3 (Yakes et al., 2011; FDA Label). These kinases are essential mediators of signal transduction pathways that govern cell proliferation, survival, migration, and angiogenesis (UniProt P08581, P35968). In various malignancies, these kinases are frequently dysregulated through overexpression or mutation, facilitating tumor progression and the development of a metastatic phenotype (Xiang et al., 2014). A key therapeutic advantage of targeting this specific group is the simultaneous inhibition of MET and AXL, which are known to be upregulated as compensatory escape mechanisms when tumors are treated with VEGF-targeted therapies alone (Zhou et al., 2016). This multi-target approach is clinically utilized to treat advanced renal cell carcinoma, hepatocellular carcinoma, and medullary thyroid cancer (StatPearls, Cabozantinib).

Other names

MET (Hepatocyte growth factor receptor)VEGFR2 (Vascular endothelial growth factor receptor 2)AXL receptor tyrosine kinaseRET (Rearranged during transfection)KIT (Mast/stem cell growth factor receptor Kit)FLT3 (Fms-like tyrosine kinase 3)TIE2 (TEK receptor tyrosine kinase)ROS1TYRO3MER (MERTK)

ATP-competitive inhibition of the kinase domains of MET, VEGFR2, AXL, and other related receptor tyrosine kinases.