DESCRIPTION (provided by applicant): The Program Project Grant "Targeting diet-induced promotion of Kras-initiated pancreatic adenocarcinoma" constitutes a highly collaborative, multidisciplinary research program designed to make a significant impact on the investigation of diet in the development of pancreatic cancer. A detailed understanding of the biological mechanisms of action of a typical Western-style diet, rich in fats and calories, on pancreatic cancer development can form the rationale for biologically-based practices and scientifically-founded dietary recommendations in the prevention of this disease. Our Program Project includes expertise from the UCLA campus and VA Greater Los Angeles Healthcare System - West Los Angeles (VAGLAHS-WLA). The Program is led by experienced pancreatic cancer researchers, who have organized investigative teams to develop highly interactive and synergistic research programs. Our goal is to study the mechanisms, by which a Western-style diet, rich in fats and calories, promotes pancreatic cancer development and to explore interventional, cancer-preventing strategies. Innovative animal and cell culture models and novel concepts strongly supported by a wealth of preliminary data are proposed. The Projects will focus on: Inflammatory processes in diet-induced pancreatic cancer promotion (Project 1); Chemoprevention of pancreatic cancer with antidiabetic agents (Project 2); Inefficient autophagy, mitochondrial dysfunction, and pancreatic tumorigenesis (Project 3); Alcohol abuse and metabolic syndrome promote desmoplasia of pancreatic cancer (Project 4). The projects will utilize our Shared Core Resources including the Administrative Core (with Biostatistics Sub-Core) and the Animal Core (with Pathology Sub-Core). An External Advisory Board comprised of nationally and internationally recognized translational pancreatic cancer investigators and advocates has been assembled. The Program Project is designed for maximum integration and synergy of research and key investigators, who have been collaborating over the years so that the proposed Program can be focused on the most promising investigations with the greatest translational potential and impact.

RELEVANCE: Insights gained from the proposed Program Project will be extremely valuable for understanding the tumor promoting effects of a Western-style diet, which will lead to efficacious preventive strategies and general health-promoting dietary recommendations. Successful confirmation of our hypothesis that dietary factors are sufficient to fully promote and accelerate tumor formation has the potential to shift current research and clinical practice.