PROJECT SUMMARY The Program Project Grant “Chemoprevention and mechanisms of obesity-promoted pancreatic adenocarcinoma” constitutes a highly collaborative, multidisciplinary research program designed to make a significant impact on the investigation of obesity in the development of pancreatic cancer. A detailed understanding of the biological mechanisms of action of obesity on pancreatic cancer development can form the rationale for biologically-based practices, scientifically-founded recommendations and interventional strategies in the prevention of this disease. The Program Project includes expertise from the UCLA campus and Cedars Sinai Medical Center. The Program is led by experienced pancreatic cancer researchers, who have organized investigative teams to develop highly interactive and synergistic research programs. The goal is to study the mechanisms, by which obesity 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: Adipose tissue inflammation in obesity- promoted pancreatic cancer (Project 1); Chemoprevention of pancreatic cancer with lipid-lowering and antidiabetic agents (Project 2); Role of the pancreatic fibro-inflammatory microenvironment in obesity- promoted pancreatic cancer (Project 3). The projects will utilize an Administrative Core (with Biostatistics Sub- Core) and a Shared Resource Core, the Animal and Cell Models 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 for more than 12 years so that the proposed Program can be focused on the most promising investigations with the greatest translational potential and impact.