Receptor tyrosine kinases (TYRO3, AXL, MERTK, VEGFR2, KIT, MET, RET) (RTKs)

This target profile represents a specific cluster of receptor tyrosine kinases (RTKs) that are critical drivers of tumor progression, angiogenesis, and immune evasion (Graham et al., 2014, Nat Rev Cancer). The TAM family (TYRO3, AXL, and MERTK) regulates the immune response within the tumor microenvironment by promoting the clearance of apoptotic cells (efferocytosis) and suppressing inflammatory signaling (Rothlin et al., 2015, Annu Rev Immunol). VEGFR2 is the primary mediator of vascular endothelial growth factor (VEGF)-induced angiogenesis, which is essential for tumor nutrient supply and metastasis (Ferrara et al., 2003, Nature Medicine). Other kinases in this group, such as c-Met, c-Kit, and RET, are frequently dysregulated through mutation or amplification in various cancers, including renal cell carcinoma and medullary thyroid cancer (Gherardi et al., 2012, Nat Rev Cancer). Multi-kinase inhibitors (MKIs) like cabozantinib are designed to target this broad spectrum to overcome resistance mechanisms, such as AXL-mediated bypass signaling, while simultaneously inhibiting the tumor's blood supply (Yakes et al., 2011, Mol Cancer Ther). By targeting both the tumor cells and the supporting microenvironment, these agents aim to provide more durable clinical responses in advanced malignancies.

Other names

TAM receptors (TYRO3, AXL, MERTK)Vascular endothelial growth factor receptor 2 (VEGFR2)KDRCD117 (c-Kit)HGFR (c-Met)Rearranged during transfection (RET)Proto-oncogene tyrosine-protein kinase receptor RetMast/stem cell growth factor receptor KitHepatocyte growth factor receptor

ATP-competitive inhibition of the intracellular tyrosine kinase domains of multiple receptors, preventing autophosphorylation and downstream signaling through pathways such as PI3K/AKT, MAPK/ERK, and STAT3.