Metabolism addiction in pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains largely elusive. Renewed research interest in longstanding doctrines of tumor metabolism has led to the emergence of aberrant signaling pathways as critical factors modulating central metabolic networks that fuel pancreatic tumors. Such pathways, including those of Ras signaling, glutamine-regulatory enzymes, lipid metabolism and autophagy, are directly affected by genetic mutations and extreme tumor microenvironments that typify pancreatic tumor cells. Elucidation of these metabolic networks can be expected to yield more potent therapies against this deadly disease.

Figure 1

Schematic overview of key Ras-regulated metabolic pathways that become aberrantly active in pancreatic tumor cells

Figure 2

Illustrative of RAGE/HMGB1 interaction and regulation of autophagic metabolism and promotion of cell survival in pancreatic tumor cells