c-Met: A Potential Target for Current Non-Small-Cell Lung Cancer Therapeutics

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. In early stages of NSCLC tumor development (stage I/II), surgical resection is often performed; however, when the cancer becomes metastatic, chemotherapy is most commonly implemented. Due to the fact that traditional chemotherapies result in adverse and cytotoxic effects on healthy cells in addition to NSCLC cells, targeted therapeutics have been extensively developed over recent years to combat the disease. These targeted therapies include small molecule inhibitors and monoclonal antibodies (MAbs), some of which are used as first-line treatments for NSCLC patients. Several inhibitors against the mesenchymal-epithelial transition factor (c-Met), and its ligand hepatocyte growth factor (HGF), have shown promising results in NSCLC clinical trials. For example, crizotinib, a multi-kinase inhibitor has been approved by the FDA for the treatment of ALK positive NSCLC. c-Met is known to be overexpressed, mutated and gene amplified, specifically in NSCLC, and has also been implicated in the development of resistance against other small-molecule inhibitors (e.g. EGFR). Thus, this review will discuss the current developments and usages of c-Met inhibitors in NSCLC, and their potential for future therapeutic advancement.