The focus of our projects is to understand the influence of obesity secreted cytokines (adipokines) on pancreatic cancer progression. Obesity and diabetes correlate with an increased risk for development of pancreatic cancer. The mechanisms of adipokine driven pancreatic cancer progression remains relatively unknown. We have found that adiponectin exhibits an anti-tumorigenic manner to antagonize the pro-tumorigenic actions of Leptin and IL-6. We are currently using a small molecule adiponectin receptor agonist, AdipoRon, to provide proof of evidence that adiponectin receptor agonists have anti-tumorigenic potential in pancreatic GEM and xenograft bearing mice. We are now focused on signaling mechanisms of obesity driven cancer progression, which suggest adiponectin suppresses adipokine induced RAS-ERK activity and that it blocks the secretion of pro-inflammatory chemokines from PDAC cells.