Molecular mechanisms in the development of pancreatic cancer

• Applicant: Professor Dr. Volker Fendrich
• Co-Applicants: Professor Dr. Yuval Dor; Professorin Dr. Areej Khatib
• Subject Area: General and Visceral Surgery ; Gastroenterology
• Term: from 2014 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257865444

Pancreatic ductal adenocarcinoma is one of the deadliest cancers worldwide. Despite major recent advances in the understanding of disease, major gaps remain which preclude the identification of diagnostic markers and effective drugs. In this proposal for a German-Palestinian-Israeli project, we will address two central problems in pancreatic cancer biology, relying on extensive preliminary studies of the three collaborating principal investigators. We will first apply several approaches to study the cellular origins of pancreatic cancer. Using advanced mouse models to tag and manipulate specific cell types in the pancreas, we will distinguish between the contribution of pancreatic duct and acinar cells to the formation of pancreatic cancer precursor lesions (PanIN). In addition, we will compare the global methylation pattern of human pancreatic cancer to the methylome of human duct and acinar cells to obtain insights into the origins of human disease. Second, we will examine the roles of mTOR-rpS6 signaling pathway and the BRCA2 tumor suppressor gene in the development of pancreatic cancer, with special emphasis on the common role of DNA damage, based on our preliminary studies suggesting a central function for DNA double strand breaks in both suppression and initiation of pancreatic cancer. The collaborating partners- Fendrich (Marburg), Khatib (Palestinian Authority) and Dor (Israel)- have a proven track record of joint publications, and will continue to work in close collaboration, taking advantage of their mutual complementary expertise. The studies are possible by the complementary expertise of our network.

• DFG Programme: Research Grants
• International Connection: Israel, Palestine