Highlights on the Role of Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma.

The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including , , and, most importantly, . A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the gene. Due to this fact, studying the function of and the impact of its mutations on the tumor microenvironment (TME) is a priority for understanding pancreatic cancer progression and designing novel therapeutic strategies for the treatment of the dismal disease. Despite some recent enlightening studies, there is still a wide gap in our knowledge regarding the impact of mutations on different components of the pancreatic TME. In this review, we will present an updated summary of mutant role in the initiation, progression, and modulation of the TME of pancreatic ductal adenocarcinoma (PDAC). This review will highlight the intriguing link between diabetes mellitus and PDAC, as well as vitamin D as an adjuvant effective therapy via TME modulation of PDAC. We will also discuss different ongoing clinical trials that use oncogene signaling network as therapeutic targets.