The fibrotic and inflammatory microenvironment in obesity and DM leads to momentous mechanical changes in the ECM that promote EMT and tumor growth.336,340 Specifically, the TME, rich in collagen and hyaluronic acid, increases the density and stiffness of the PC stroma, shielding cancer cells while reenforcing the inflammatory reaction.340 In mice with mutant Kras, increased severity of inflammation-induced pancreatic injury and fibrosis were suggested to accelerate carcinogenesis due to the loss of tuft cells and decreased production of prostaglandin D2. Here, KRAS is linked to obesity due to melanocortin 4 receptor deficiency.