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Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer

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Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 908))

Abstract

This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis. We critically examine the rationale behind specific GEMMs, chemical carcinogens, dietary promoters, Helicobacter infection, and direct mutagenesis of relevant oncogenes and tumor suppressor that have been developed to study gastric cancer pathogenesis. Despite species differences, more efficient and effective models to test specific genes and pathways disrupted in human gastric carcinogenesis have yet to emerge. As we better understand these species differences, “humanized” versions of mouse models will more closely approximate human gastric cancer pathogenesis. Towards that end, epigenetic marks on chromatin, the gut microbiota, and ways of manipulating the immune system will likely move center stage, permitting greater overlap between rodent and human cancer phenotypes thus providing a unified progression model.

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Acknowledgements

We would like to acknowledge support from NIH Grant P01-DK64041 (to JLM).

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Authors and Affiliations

  1. Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA

    Lin Ding & Juanita L. Merchant M.D., Ph.D.

  2. Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan, 1150 West Medical Center Drive, 6518 MSRB 1, Ann Arbor, MI, 48109-5682, USA

    Mohamad El Zaatari

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  1. Lin Ding
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  2. Mohamad El Zaatari
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  3. Juanita L. Merchant M.D., Ph.D.
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Correspondence to Juanita L. Merchant M.D., Ph.D. .

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  1. UCL Cancer Institute, University College London, London, United Kingdom

    Marnix Jansen

  2. Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom

    Nicholas A. Wright

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Ding, L., El Zaatari, M., Merchant, J.L. (2016). Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer. In: Jansen, M., Wright, N. (eds) Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract. Advances in Experimental Medicine and Biology, vol 908. Springer, Cham. https://doi.org/10.1007/978-3-319-41388-4_22

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