Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 16, 2015; 3(1): 42-51
Published online Jan 16, 2015. doi: 10.12998/wjcc.v3.i1.42
Recent advances in the HER2 targeted therapy of gastric cancer
Tasuku Matsuoka, Masakazu Yashiro
Tasuku Matsuoka, Masakazu Yashiro, Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
Masakazu Yashiro, Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
Author contributions: Matsuoka T and Yashiro M designed this review; Matsuoka T wrote the manuscript; Yashiro M edited manuscript.
Supported by KAKENHI (Grant-in-Aid for Scientific Research), No. 23390329; and the National Cancer Center Research and Development Fund (23-A-9).
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: Masakazu Yashiro, MD, Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Telephone: +81-6-66453838 Fax: +81-6-66466450
Received: August 4, 2014
Peer-review started: August 6, 2014
First decision: September 16, 2014
Revised: October 9, 2014
Accepted: November 17, 2014
Article in press: December 23, 2014
Published online: January 16, 2015

Recent advances in molecular targeted therapies, including targeting human epidermal growth factor receptor 2 (HER2), had a major forward step in the therapy for gastric cancer patients. Application of HER2-targeted therapies, in particular trastuzumab in combination with chemotherapy in metastatic HER2-positive gastric cancers, resulted in improvements in response rates, time to progression and overall survival. Nevertheless, as with breast cancer, many patients with gastric cancer develop resistance to trastuzumab. Several promising therapies are currently being developed in combination with chemotherapy to increase the efficacy and overcome the cancer-resistance. Here we review the current overview of clinical application of agents targeting HER2 in gastric cancer. We also discuss the ongoing trials supporting the use of HER2-targeted agents combined with cytotoxic agents or other monoclonal antibodies.

Keywords: Human epidermal growth factor receptor 2, Gastric cancer, Targeting therapy, Trastuzumab

Core tip: This review summarizes the development of diagnostic and therapeutic approach for the patients with human epidermal growth factor receptor 2 (HER2)-overexpressed/amplified gastric cancer. The biology of HER2-dependent signalling is also described. The ToGA trial highlighted the importance of accurate HER2 testing to guide treatment choice of gastric cancer. Future strategies beyond the ToGA trial to address EFGR family, including HER2 pathway are discussed according to current ongoing clinical trials, as well as experimental studies.