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Targeting HER2 amplifications in gastric cancer

Authors Ung L, Chua T, Merrett N

Received 7 November 2013

Accepted for publication 27 November 2013

Published 31 January 2014 Volume 2014:4 Pages 11—22

DOI https://doi.org/10.2147/GICTT.S57199

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3


Lawson Ung, Terence C Chua, Neil D Merrett

Department of Surgery, South Western Sydney Upper GI Surgical Unit, Bankstown Hospital, University of Western Sydney, Sydney, NSW, Australia

Abstract: While multimodality treatments, including neoadjuvant and adjuvant chemotherapy or chemoradiation, have become the global standard of care in patients with locally advanced and metastatic gastric cancers (GCs), long-term outcomes for patients remain poor. This reflects the aggressive tumor biology of GCs and occult nature of the disease, often presenting in its advanced stages, as well as the challenges of developing effective targeted therapy to treat this disease. The Trastuzumab for Gastric Cancer trial demonstrates that the addition of human epidermal growth factor 2 (HER2) monoclonal antibody trastuzumab to standard chemotherapy regimen consisting of 5-fluorouracil (5-FU) or capecitabine with cisplatin results in significant improvement in overall and progression-free survival. Although questions remain regarding the best methods by which to determine HER2 mutation positivity and amplification, through immunohistochemistry or in situ hybridization, and whether trastuzumab is effective for locally advanced, nonmetastatic GC in an adjuvant setting, the trial has led to a surge of clinical trials investigating the potential role of other HER2- and non-HER2-targeted therapies to improve patient outcomes. This review will discuss our current understanding of GC pathogenesis, current available treatments, and the potential impact that targeting HER2 amplifications may have in our efforts to individualize and optimize cancer care in GC individuals.

Keywords: Personalized cancer therapy, surgical oncology, gastrectomy, adjuvant treatment, targeted therapies

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