Pancreatic Cancer: Basic Mechanisms and Therapies, Volume 159 in the Advances in Cancer Research, presents the latest release in this ongoing, well-regarded serial with invaluable information on the exciting and fast-moving field of cancer research. Pancreatic cancer (PC) is the third leading cause of cancer-related deaths in the United States. Greater than 90% PCs are Pancreatic ductal adenocarcinomas (PDAC) which have a dismal estimated 5-year overall survival of only 11%. PDAC is predicted to become the second leading cause of mortality in the United States by 2030. In the clinic, the PDAC patients often present with incurable disease at the time of first diagnosis. This cancer is particularly lethal because of its propensity to spread quickly to distant organs including the lymphatic system. PDAC metastasis occurs shortly after tumor initiation and is caused by a complex interaction between autonomous tumor cells and cellular elements of the tumor microenvironment. Although PDAC remains a challenging disease to treat and a leading cause of cancer-related deaths, progress is being made in disease etiology and pathogenesis, and intensive research is focused on developing optimal treatment approaches for patients. Considering the continuous progress being made in understanding PDAC pathogenesis and designing new therapies, it was considered timely to develop an up-to-date thematic issue of Advances in Cancer Research (ACR) focused on PDAC. In this thematic issue, we have included ten review articles by experts that cover cancer disparities, PDAC pathobiology, the roles of the tumor microenvironment, tumor heterogeneity, PC stem cells, genetic and signaling events critical for PDAC pathogenesis, Immunotherapy and chemoresistance in PDAC, and different PDAC mouse models. This special issue highlights recent research progress in PDAC, which bridges the gap between basic and clinical research.