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Annals of Oncology Advance Access originally published online on April 25, 2008
Annals of Oncology 2008 19(9):1523-1529; doi:10.1093/annonc/mdn169
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

reviews

HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target

C. Gravalos1,* and A. Jimeno2

1 Medical Oncology Department, University Hospital "12 de Octubre", Madrid, Spain
2 Developmental Therapeutics/Pharmacodynamic Laboratory, University of Colorado Cancer Center, Aurora, CO, 80045 USA

* Correspondence to: Dr C. Gravalos, Servicio de Oncología Médica, Hospital Universitario 12 de Octubre, Avda. de Andalucía s/n Km 5.400, 28041 Madrid, Spain. Tel: +34-91-390-83-49; Fax: +34-91-460-33-10; E-mail: cgravalos{at}telefonica.net

Gastric cancer is the second leading cause of cancer mortality in the world and its management, especially in advanced stages, has evolved relatively little. In particular, no targeted modality has so far been incorporated to its treatment armamentarium. HER2 overexpression is increasingly recognized as a frequent molecular abnormality, driven as in breast cancer by gene amplification. There is mounting evidence of the role of HER2 overexpression in patients with gastric cancer, and it has been solidly correlated to poor outcomes and a more aggressive disease. Additionally, preclinical data are showing significant antitumor efficacy of anti-HER2 therapies (particularly monoclonal antibodies directed towards the protein) in in vitro and in vivo models of gastric cancer. As a result, several clinical trials are exploring in different settings and with diverse designs the potential of anti-HER2 therapies in gastric cancer patients. This review summarizes the rationale, preclinical evidence, retrospective clinical analyses, and the interim clinical data pertaining HER2 therapies in gastric cancer.

Key words: c-ErbB-2, gastric cancer, gastroesophageal adenocarcinoma, HER2, prognostic factor, trastuzumab

Received for publication January 29, 2008. Revision received April 13, 2008. Accepted for publication March 20, 2008.


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