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World J Clin Oncol. May 10, 2011; 2(5): 195-202
Published online May 10, 2011. doi: 10.5306/wjco.v2.i5.195
Genetically-engineered mouse models for pancreatic cancer: Advances and current limitations
Hideaki Ijichi
Hideaki Ijichi, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
Author contributions: Ijichi H designed and wrote the manuscript.
Correspondence to: Dr. Hideaki Ijichi, MD, PhD, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. hideijichi-gi@umin.ac.jp
Telephone: +81-3-38155411 Fax: +81-3-38140021
Received: November 30, 2010
Revised: April 17, 2011
Accepted: April 24, 2011
Published online: May 10, 2011
Abstract

Recently, there has been significant progress in the development of genetically-engineered mouse (GEM) models. By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse pancreas, animal models can recapitulate human disease. Pancreas epithelium-specific endogenous Kras activation develops murine pancreatic intraepithelial neoplasia (mPanIN). Additional inactivation of p16, p53, or transforming growth factor-β signaling, in the context of Kras activation, dramatically accelerates mPanIN progression to invasive pancreatic ductal adenocarcinoma (PDAC) with abundant stromal expansion and marked fibrosis (desmoplasia). The autochthonous cancer models retain tumor progression processes from pre-cancer to cancer as well as the intact tumor microenvironment, which is superior to xenograft models, although there are some limitations and differences from human PDAC. By fully studying GEM models, we can understand the mechanisms of PDAC formation and progression more precisely, which will lead us to a breakthrough in novel diagnostic and therapeutic methods as well as identification of the origin of PDAC.

Keywords: Pancreatic ductal adenocarcinoma; Genetically-engineered mouse; Pancreas epithelium-specific; Kras; Tumor-stromal interaction; Tumor microenvironment; Origin of pancreatic ductal adenocarcinoma; Murine pancreatic intraepithelial neoplasia; Acinar-ductal metaplasia; Inducible genetically-engineered mouse