Mitochondrial reprogramming as a central driver of pancreatic ductal adenocarcinoma

Pancreatic cancer has recently been observed to have a rise in incidence and prevalence in terms of cancer-related mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent type of pancreatic cancer and is considered highly aggressive. Although recent advancements in chemotherapy, radiation therapy, and immunotherapy provide increased options for treatment, the survival rate of pancreatic cancer compared to other types of malignancies is still relatively low. Especially for PDAC, surgical resection is the only curative therapy considered, but most of these tumors are diagnosed at an advanced stage and are therefore ineligible for surgery. Emerging evidence demonstrates that mitochondrial reprogramming is a central driver of PDAC progression, influencing metabolic plasticity, redox balance, mitochondrial dynamics, and therapy resistance. This review discusses how mitochondrial changes promote PDAC and emerging therapies targeting mitochondria, particularly those that modulate mitochondrial function and metabolism. A deeper understanding of mitochondrial reprogramming may provide novel biomarkers and therapeutic opportunities, ultimately improving early detection and treatment outcomes in PDAC.