Figure 1.

KRas-driven ROS homeostasis and its role in the development of pancreatic cancer. Acquisition of an oncogenic KRas mutation in pancreatic acinar cells leads to their transdifferentiation to duct-like cells. This process named acinar-to-ductal metaplasia (ADM) forms the precursor to PanIN lesions. KRas-induced formation of ROS, due to changes in the cell's metabolic programs, is involved in both ADM and growth and progression of PanIN lesions. A key issue for precancerous and cancer cells is to keep ROS at levels where they are beneficial for tumor development or progression, but below the threshold that leads to induction of senescence or cell death. In KRas-driven neoplasia aberrantly increased ROS levels are therefore accompanied by an upregulation of antioxidant genes.