Hepatocyte growth factor receptor (MET) (MET)

Hepatocyte growth factor receptor (MET) is a transmembrane receptor tyrosine kinase (RTK) primarily expressed on epithelial cells and is activated by its sole high-affinity ligand, hepatocyte growth factor (HGF) [3, 8, 18]. The HGF/MET axis is essential for normal physiological processes, including embryonic development, organogenesis, and wound healing, by orchestrating "invasive growth" programs that involve cell proliferation, survival, and motility [12, 14, 26, 28]. In many human cancers, the pathway is pathologically activated through MET gene amplification, overexpression, or specific mutations such as MET exon 14 skipping, which lead to constitutive kinase activity and aggressive tumor behavior [4, 7, 18, 26]. Dysregulated MET signaling is a well-established driver of tumor metastasis and is frequently implicated in resistance to other targeted therapies, such as EGFR inhibitors in lung cancer [6, 9, 11, 18]. Consequently, MET has emerged as a major therapeutic target, with several approved small-molecule tyrosine kinase inhibitors and ongoing development of monoclonal antibodies and antibody-drug conjugates designed to disrupt this oncogenic signaling [10, 18, 21].

Other names

c-MetMETHGFRHepatocyte growth factor receptorHGF receptorProto-oncogene c-MetTyrosine-protein kinase MetScatter factor receptorAUTS9RCCP2

Inhibition of MET tyrosine kinase activity (ATP-competitive or non-competitive small molecules); Neutralization of the HGF ligand; Blockade of MET receptor dimerization; Induction of MET receptor degradation; Antibody-drug conjugate-mediated cytotoxicity [10, 12, 18, 20, 21].