Fig. 7: Schematic model displaying the metabolic reprogramming induced by DCK inactivation.

One of the major factors contributing to gemcitabine resistance is DCK inactivation. Following DCK deletion, PDAC cells exhibited an enhanced reliance to OXPHOS, leading to an increased ATP production within the mitochondria. This metabolic shift renders the cells less glycolytic in nature. Moreover, DCK function loss leads to mitochondrial morphology alterations. Heightened dependence on OXPHOS results in elevated ROS production. To counteract the potential harmful effects of ROS, antioxidant levels of the enzymes SOD1 and SOD2 are increased in DCK-deficient PDAC cells, which stabilizes the cells and reduces the instability induced by the increased ROS.