FIGURE 3.

Oxidative stress response determines pancreatic ductal adenocarcinoma (PDAC) cell survival in the tumor microenvironment. The tumor microenvironment augments cancer metabolic flows of glycolysis and glutaminolysis; the former contributes to the Warburg effect and activation of PPP, which gives rise to the production of biomass such as nucleotides and lipids. The dysfunction of SIRT3 results in the stimulation of the HIF pathway, whereas the dysfunction of SIRT6 induces the transcription of glycolytic genes and glutaminase. The inevitable production of ROS from the mitochondria of living cells was reduced by GSH, which can lead to ferroptosis. The response to oxidative stress determines cell survival or death, which may contribute to clonal evolution. aKG, alpha‐ketoglutarate; CD44v, CD44 variant; GPX4, glutathione peroxidase 4; GSH, reduced glutathione, lipid‐OOH, lipid hydroperoxide; HIF1a, hypoxia‐inducible factor 1 subunit alpha; MYC, MYC proto‐oncogene, basic helix‐loop‐helix (BHLH) transcription factor; PPP, pentose phosphate pathway; ROS, reactive oxygen species; TCA, tricarboxylic acid cycle