Published online Nov 15, 2015. doi: 10.4251/wjgo.v7.i11.317
Peer-review started: February 26, 2015
First decision: March 30, 2015
Revised: April 6, 2015
Accepted: August 25, 2015
Article in press: August 28, 2015
Published online: November 15, 2015
Processing time: 265 Days and 14.3 Hours
Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.
Core tip: MET protein overexpression or MET gene amplification was associated with tumor progression and survival in gastric cancer (GC), although the definition of MET overexpression remains to be standardized. In preclinical studies, MET antibodies or small-molecule MET inhibitors suppressed cell proliferation and tumor progression in MET-amplified GC cells. Therefore, MET-targeting therapy is promising, and MET overexpression might be a useful biomarker of the response to chemotherapy inhibiting MET. Some clinical trials of MET inhibitors were conducted in metastatic GC, but sufficient benefits have not been demonstrated yet.