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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2016; 22(3): 1179-1189
Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.1179
Changing strategies for target therapy in gastric cancer
Suk-young Lee, Sang Cheul Oh
Suk-young Lee, Sang Cheul Oh, Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Guro-gu, Seoul 08308, South Korea
Author contributions: Lee S wrote the manuscript; Oh SC edited the manuscript.
Supported by The Technology Innovation Program, No. 10041653, funded by the Ministry of Trade, Industry and Energy (MI, Korea); and Korea University Grant, No. K1220401.
Conflict-of-interest statement: The authors declared no conflict of interest related to this study.
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:
Correspondence to: Sang Cheul Oh, MD, PhD, Professor of Internal Medicine, Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, 148 Gurodong-ro, Guro-gu, Seoul 08308, South Korea.
Telephone: +82-2-26263060 Fax: +82-2-8626453
Received: April 28, 2015
Peer-review started: May 7, 2015
First decision: August 25, 2015
Revised: September 8, 2015
Accepted: November 13, 2015
Article in press: November 13, 2015
Published online: January 21, 2016

In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer.

Keywords: Advanced gastric cancer, Target therapy, Chemotherapy, Strategy, Signal pathway

Core tip: This review summarizes the development of molecular targeted therapeutic agents in advanced gastric cancer. Agents targeting angiogenesis as well as ERBB receptors and their downstream signaling pathways are introduced. Current efforts to overcome resistance to the human epidermal growth factor receptor 2-targeted agents are also presented from the ongoing clinical trials. Future direction of target therapy should be guided according to further clarification of the molecular mechanisms of gastric cancer and by exploring appropriate indications for application of molecular targeted therapy to improve its efficacy.