Abstract
Recently, by using pancreas-specific conditional activation or knockout of clinically relevant pancreatic cancer-related genes and signaling pathways, genetically engineered murine models(GEMs) of pancreatic ductal adenocarcinoma have been developed. Pancreas-specific Kras activation results in mouse PanIN(pancreatic intraepithelial neoplasia) lesions. Further, simultaneous inactivation of either tumor suppressor pathway (p16, p53, or TGF-β signal) dramatically accelerates the tumor progression into invasive cancer. The tumor demonstrates ductal adenocarcinoma with abundant stromal expansion including marked fibrosis, desmoplasia, which recapitulates the human disease very well.
These genetically-engineered models have an advantage over xenograft models in that they recapitulate multi-step carcinogenesis and the tumor microenvironment of human disease.
Detailed analysis of current and future GEMs will provide better understanding of pancreatic carcinogenesis and progression as well as of the origin of pancreatic cancer, leading to refined methods for its diagnosis, therapy and prevention.
