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  • Review Article
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Anti-HER agents in gastric cancer: from bench to bedside

Nature Reviews Gastroenterology & Hepatology volume 8, pages 369–383 (2011)Cite this article

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Abstract

Despite some advances in the past few years, the search for effective treatment modalities for advanced gastric and gastro-esophageal junction cancer is far from over. Available data clearly demonstrate that the development of new drugs will have little, if any, chance of success if it is not guided by in-depth knowledge of disease biology. However, using biologic agents to target key molecular pathways, such as those regulated by human epidermal growth factor receptor (HER) family members, may be effective. Indeed, the positive results achieved by the anti-HER2 agent trastuzumab in a phase III trial in HER2-positive patients support this approach. Many new anti-HER molecules are now under evaluation for the treatment of gastric and gastro-esophageal junction cancer, but so far attempts to identify reliable predictive factors from phase I and II trials have produced inconclusive results. In addition, large phase III trials are still being conducted in molecularly unselected populations. Refining patient selection is essential to maximize the benefit of targeted agents, to avoid significant toxicities and for the development of alternative therapeutic approaches in patients who have nonresponsive disease.

Key Points

  • Human epidermal growth factor receptor (HER) family members are the target of multiple biologic agents currently under investigation for the treatment of gastric and gastro-esophageal junction cancer

  • The combination of trastuzumab and chemotherapy has demonstrated improved efficacy compared with chemotherapy alone, paving the way for new treatment modalities in subsets of patients with gastric cancer

  • Evaluation of HER2 status by immunohistochemistry or fluorescent in situ hybridization does not represent a definitive selection parameter for treatment, as not all HER2-positive patients respond to treatment

  • Additional potential biomarkers for anti-HER2 therapies are still to be defined and may represent promising targets for novel therapeutics

  • Many anti-EGFR (epidermal growth factor receptor) agents are at advanced stages of clinical development, but attempts to identify responsive patients on the basis of molecular parameters have been disappointing

  • The development of biologic agents for use in highly selected patient subsets should represent a new paradigm for the treatment of gastric and gastro-esophageal junction cancer

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Figure 1: The main transduction pathways regulated by the four HER family members—EGFR, HER2, HER3, and HER4.

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Acknowledgements

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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  1. U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano-Tumori, Via Roma 67, 56126, Pisa, Italy

    Lorenzo Fornaro, Maurizio Lucchesi, Chiara Caparello, Enrico Vasile, Sara Caponi, Laura Ginocchi, Gianluca Masi & Alfredo Falcone

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  1. Lorenzo Fornaro
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L. Fornaro and M. Lucchesi contributed equally to the research, discussion, writing and editing of this manuscript. C. Caparello contributed to the research, discussion and editing of the manuscript. E. Vasile, S. Caponi, L. Ginocchi, G. Masi and A. Falcone contributed to the discussion and editing of the manuscript.

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Correspondence to Lorenzo Fornaro.

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Fornaro, L., Lucchesi, M., Caparello, C. et al. Anti-HER agents in gastric cancer: from bench to bedside. Nat Rev Gastroenterol Hepatol 8, 369–383 (2011). https://doi.org/10.1038/nrgastro.2011.81

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