Regulation of Pancreatic Tumorigenesis by Necroptosis

• Applicant: Dr. Berk Aykut
• Subject Area: General and Visceral Surgery
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 310966317

Pancreatic ductal adenocarcinoma is a highly aggressive disease and represents the fourth leading cause of cancer-related death among both women and men in Germany. Despite recent advances in the field of cancer diagnostics that enabled early detection, our understanding of the fundamental mechanisms orchestrating cell growth and death in pancreatic cancer remains limited. The proposed project will elucidate the role of necroptosis in pancreatic tumorigenesis. Necroptosis denotes a programmed form of necrosis, or inflammatory cell death. By contrast to apoptosis, of which disruption is widely regarded as a basic cancer cell surviving modality, necrotic cell death culminates in cellular leakage that is a strong trigger of adaptive and innate immune responses. The presented research project will: 1) evaluate the significance of necroptosis in pancreatic cancer 2) examine if modulating necroptosis alters the biology of pancreatic cancer and 3) characterize the effects of modulating necroptosis in pancreatic cancer. Based on preliminary data, we postulate that, interfering in the interplay between the inflammatory and epithelial compartment in pancreatic cancer by manipulating the necrosome can alter the rate of pancreatic carcinogenesis in vivo an may expose a new target for experimental therapeutics in pancreatic cancer. Implicating necroptosis in pancreatic tumor cell death and chemosensibility or resistance is highly novel and presents a paradigm shift for understanding the mechanism of pancreatic cancer cell death.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. George Miller