The role of mesenchymal-epithelial transition factor (c-MET) in cancer development and treatments

Abstract

The mesenchymal-epithelial transition factor (c-MET) is classified into the tyrosine kinase receptor family. Its indispensable role in regulating the cell cycle through various downstream pathways has made it one of the most essential transmembrane receptors. A MET receptor monomer contains six domains, and each has its own function when activated by hepatocyte growth factor (HGF). Due to its complexity, c-MET aberrations including point mutations, amplification, protein overexpression, splicing site mutation, fusion, and HGF autocrine or paracrine upregulate cell proliferation and are common in most aggressive cancer types such as colorectal cancer, lung cancer, liver cancer, and glioblastoma. Correspondingly, cancer therapies targeting c-MET have been researched for decades. This review presented the mechanisms under c-MET activation, discussed its role in cancer development, and summarized recent advancements in clinical trials. c-MET inhibitors, especially combined with other therapeutic inhibitors, appeared to be a promising strategy when taking selectivity, resistance, and tolerability into account.