Hepatocyte growth factor receptor (c-MET) (c-MET)

The Hepatocyte growth factor receptor, commonly known as c-MET, is a transmembrane receptor tyrosine kinase that is activated by its sole ligand, Hepatocyte growth factor (HGF) [1, 2]. This signaling axis plays a fundamental role in embryonic development, tissue regeneration, and wound healing by regulating cellular processes such as proliferation, motility, and survival [7, 14, 16]. In many human malignancies, the c-MET/HGF pathway is aberrantly activated through gene amplification, overexpression, or specific mutations, such as MET exon 14 skipping, which drive tumor progression, metastasis, and angiogenesis [1, 12, 17]. Furthermore, c-MET activation is a well-recognized mechanism of acquired resistance to other targeted therapies, particularly epidermal growth factor receptor (EGFR) inhibitors in non-small cell lung cancer [12, 17]. Therapeutic strategies targeting this pathway include small-molecule tyrosine kinase inhibitors that block the receptor's catalytic activity, monoclonal antibodies that neutralize HGF or the receptor itself, and bispecific antibodies [3, 10, 11]. Clinical management of c-MET-driven cancers relies on biomarkers like MET amplification and mutations to identify patients most likely to benefit from these targeted interventions [14, 17].

Other names

METHGFRMesenchymal-epithelial transition factorProto-oncogene c-MetHGF receptorTyrosine-protein kinase METAUTS9RCCP2

Therapeutic agents targeting the c-MET/HGF axis operate through several distinct mechanisms: small-molecule tyrosine kinase inhibitors (TKIs) block the intracellular catalytic activity of the c-MET receptor by competing with ATP; monoclonal antibodies target the extracellular domain of c-MET to prevent ligand binding, induce receptor internalization, or trigger antibody-dependent cellular cytotoxicity; and ligand-neutralizing antibodies bind directly to HGF to prevent its interaction with the receptor [3, 10, 11, 13].