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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2015; 7(11): 317-327
Published online Nov 15, 2015. doi: 10.4251/wjgo.v7.i11.317
Clinical significance of MET in gastric cancer
Mikito Inokuchi, Sho Otsuki, Yoshitaka Fujimori, Yuya Sato, Masatoshi Nakagawa, Kazuyuki Kojima
Mikito Inokuchi, Sho Otsuki, Yoshitaka Fujimori, Yuya Sato, Masatoshi Nakagawa, Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Kazuyuki Kojima, Department of Minimally Invasive Surgery, Tokyo Medical and Dental University, Tokyo 113-8519, Japan
Author contributions: Inokuchi M and Kojima K contributed to writing this manuscript; Nakagawa M, Otsuki S, Fujimori Y and Sato Y contributed to gathering, reviewing, and analyzing the related literature.
Conflict-of-interest statement: The authors have declared that they have no competing financial interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mikito Inokuchi, MD, PhD, Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. m-inokuchi.srg2@tmd.ac.jp
Telephone: +81-35-8035261 Fax: +81-35-8030139
Received: February 24, 2015
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
Abstract

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.

Keywords: MET; Gastric cancer; Genomic amplification; Immunohistochemistry; Clinical trial

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.