Hepatocyte growth factor receptor (MET) (MET)

Hepatocyte growth factor receptor, commonly known as MET kinase, is a transmembrane receptor tyrosine kinase that serves as the sole high-affinity receptor for hepatocyte growth factor (HGF) [6, 7, 18]. Upon ligand binding, MET undergoes dimerization and autophosphorylation, triggering intracellular signaling cascades such as the PI3K/AKT, MAPK/ERK, and STAT3 pathways [11, 13, 23]. These pathways are essential for normal physiological processes, including embryonic development, organogenesis, wound healing, and tissue regeneration [13, 15]. However, dysregulation of MET through gene amplification, point mutations (such as exon 14 skipping), or protein overexpression is a frequent driver of tumor progression, epithelial-mesenchymal transition (EMT), and metastasis in various malignancies [9, 11, 18]. In the context of oncology, MET signaling is often implicated in the development of resistance to other targeted therapies, particularly those inhibiting the vascular endothelial growth factor (VEGF) pathway [3, 4]. Cabozantinib is a potent, small-molecule multi-kinase inhibitor that targets MET, VEGFR2, and AXL, among other kinases [1, 2, 17]. By simultaneously inhibiting these pathways, cabozantinib effectively suppresses tumor angiogenesis, invasiveness, and metastatic spread [1, 4, 25]. It is clinically approved for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma, and medullary thyroid cancer, where MET inhibition plays a crucial role in overcoming therapeutic resistance and improving patient outcomes [3, 4, 16].

Other names

c-MetHGFRMET proto-oncogeneReceptor tyrosine kinaseAUTS9RCCP2DFNB97OSFD

Multi-kinase inhibitor targeting MET, VEGFR1/2/3, AXL, RET, KIT, FLT3, TIE2, ROS1, TYRO3, MER, and TRKB