Abstract: Pancreatic ductal adenocarcinoma is the most common pancreatic neoplasm with characteristics of latent morbidit, poor prognosis, high mortality rate, and limited treatments. Many studies focused on its pathogenesis, and showed molecular genetic alterations, which derived of genetic and environmental factors, played an important role in tumorigenesis. Recently, more and more findings laid particular emphasis on the level of gene molecule and some were confirmed in vitro and vivo. In this paper, we made a review and summarized the marked molecular changes and signalings of the major four pathways to understand their functions in PDAC.