Cells of origin of pancreatic neoplasms

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease associated with poor prognosis, despite recent medical advances. It is of great importance to understand the initial events and cells of origin of pancreatic cancer to prevent the development and progression of PDAC. There are three distinct precursor lesions that develop into PDAC: pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs). Studies on genetically engineered mouse models have revealed that the initiation and development of these lesions largely depend on genetic alterations. These lesions originate from different populations in the pancreas. PanIN development seems to be the result of the transdifferentiation of acinar cells, whereas IPMNs most likely arise from the progenitor niche of the pancreatic ductal epithelium. Pancreatic carcinogenesis is dependent on various events, including gene alterations, environmental insults, and cell types. However, further studies are needed to fully understand the initial processes of pancreatic cancer.