C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.

The high incidence and mortality rates of tumors have resulted in significant social and economic burdens, posing a major global threat to human life and societal development. In recent years, molecular targeted therapy for tumors has become a research hotspot. C-MET, the receptor for hepatocyte growth factor (HGF), plays a crucial role in the HGF/C-MET signaling pathway, which is involved in various processes such as tumor cell growth, invasion, migration, angiogenesis, epithelial-mesenchymal transition, tumor microenvironment remodeling and therapeutic resistance. Several C-MET-targeting strategies have been developed, including small-molecule tyrosine kinase inhibitors (TKIs), monoclonal antibodies (mAbs) against C-MET or HGF, antibody-drug conjugates (ADCs), nucleic acid aptamers, soluble receptors, natural compounds, and proteolysis targeting chimeras (PROTACs) targeting MET. These inhibitors have demonstrated encouraging anti-tumor effects in both preclinical and clinical studies, with several already available on the market. However, further research is still needed on the activation mechanisms of the HGF/C-MET signaling pathway and its interactions with other receptor tyrosine kinases, which will aid in identifying suitable patients for these treatments. This review provides a comprehensive overview of the structure, regulation, signaling pathways, and functions of C-MET, along with recent advances in C-MET inhibitors, offering valuable insights for cancer therapy.