Genetically-engineered mouse models for pancreatic cancer: Advances and current limitations.

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.