Impact of physical activity and obesity on early pancreatic carcinogenesis

• Applicant: Dr. Laura Roth
• Subject Area: Endocrinology, Diabetology, Metabolism ; Gastroenterology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 507975958

Associated with an appallingly low 5-year survival rate of 8%, pancreatic cancer exhibits the worst prognosis of all solid tumors. Moreover, the PDAC incidence steadily increases in the Western world for poorly understood reasons. Increasing incidence and a lack of satisfying treatment options will cause PDAC to be the second-leading cause of cancer-related deaths in the western world by 2030. Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and develops via precursor lesions (pancreatic intraepithelial neoplasia = PanIN). In human PDAC, obesity represents one of the most significant risk factors. A close connection between the increasing prevalence of obesity and the rising incidence of PDAC seems to be likely. Obesity arises from an impaired energy balance caused by an increased caloric intake and/or reduced calorie consumption. Obesity is often associated with reduced physical activity. Adipose and muscle tissues are both endocrine organs. Hormones produced by these organs are classified as adipokines and myokines, respectively, with both mediating multiple systemic effects. In contrast, the myokine irisin is a mediator of physical activity, and has been implicated in antiproliferative effects on several tumor cells. The project is focused on the impact of both physical activity on the one hand and obesity on the other during early pancreatic carcinogenesis. Effects on precursor lesions on a molecular level will be studied, by applying several in vitro and in vivo models. Our goal is to improve our understanding of molecular mechanisms triggered by physical activity and obesity on early pancreatic carcinogenesis to develop novel approaches of prevention and early detection.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Bruce M. Spiegelman