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Pancreatic cancer (PC) is one of the most aggressive solid malignancies, with an overall 5-year survival rate of 8%, and it is predicted to become the second leading cause of cancer-related death by 2030. PC progression and metastasis are strongly influenced by metabolic stress imposed by the tumor microenvironment (TME) due to limited oxygen and nutrient supply and unfavorable pH. In this context, deregulation and the reprogramming of energy metabolism are hallmarks of PC, which leads tumor cells to rewire their glucose, amino acid, and lipid metabolism on the basis of the bioenergetic and biosynthetic demands needed to survive and escape immunosurveillance. For this reason, exploiting cellular plasticity through the targeted reprogramming of metabolic features in PC could lead to the generation of promising and novel selective therapeutic approaches for patients' treatment.
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