Metabolic plasticity in heterogeneous pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignant neoplasms. The recognized hallmarks of PDA are regarded to be downstream events of metabolic reprogramming. Because PDA is a heterogeneous disease that is influenced by genetic polymorphisms and changes in the microenvironment, metabolic plasticity is a novel feature of PDA. As intrinsic factors for metabolic plasticity, K-ras activation and mutations in other tumor suppressor genes induce abnormal mitochondrial metabolism and enhance glycolysis, with alterations in glutamine and lipid metabolism. As extrinsic factors, the acidic and oxygen/nutrient-deprived microenvironment also induces cancer cells to reprogram their metabolic pathway and hijack stromal cells (mainly cancer-associated fibroblasts and immunocytes) to communicate, thereby adapting to metabolic stress. Therefore, a better understanding of the metabolic features of PDA will contribute to the development of novel diagnostic and therapeutic strategies.