Cellular metabolism in pancreatic cancer as a tool for prognosis and treatment (Review)
Affiliations: Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, 10000 Prague, Czech Republic
- Published online on: June 20, 2022 https://doi.org/10.3892/ijo.2022.5383
Copyright: © Zuzčák
et al. This is an open access article distributed under the
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Pancreatic cancer (PC) has one of the highest fatality rates and the currently available therapeutic options are not sufficient to improve its overall poor prognosis. In addition to insufficient effectiveness of anticancer treatments, the lack of clear early symptoms and early metastatic spread maintain the PC survival rates at a low level. Metabolic reprogramming is among the hallmarks of cancer and could be exploited for the diagnosis and treatment of PC. PC is characterized by its heterogeneity and, apart from molecular subtypes, the identification of metabolic subtypes in PC could aid in the development of more individualized therapeutic approaches and may lead to improved clinical outcomes. In addition to the deregulated utilization of glucose in aerobic glycolysis, PC cells can use a wide range of substrates, including branched‑chain amino acids, glutamine and lipids to fulfil their energy requirements, as well as biosynthetic needs. The tumor microenvironment in PC supports tumor growth, metastatic spread, treatment resistance and the suppression of the host immune response. Moreover, reciprocal interactions between cancer and stromal cells enhance their metabolic reprogramming. PC stem cells (PCSCs) with an increased resistance and distinct metabolic properties are associated with disease relapses and cancer spread, and represent another significant candidate for therapeutic targeting. The present review discusses the metabolic signatures observed in PC, a disease with a multifaceted and often transient metabolic landscape. In addition, the metabolic pathways utilized by PC cells, as well as stromal cells are discussed, providing examples of how they could present novel targets for therapeutic interventions and elaborating on how interactions between the various cell types affect their metabolism. Furthermore, the importance of PCSCs is discussed, focusing specifically on their metabolic adaptations.