Therefore, a detailed understanding of the vulnerability of the pancreas to exogenous risk factors during PDAC development and the underlying mechanisms of the interplay between oncogenic KRAS and the environmental risk factors, including obesity, chronic HFD, and inflammation, are critical for the design of novel, effective targeting strategies for the prevention and therapy of pancreatic cancer. This evidence concerns the gene KRAS and obesity due to melanocortin 4 receptor deficiency.