Targeting the Metabolic Rewiring in Pancreatic Cancer and Its Tumor Microenvironment.

Cancers (Basel)

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-8655, Tokyo, Japan.

Published: September 2022

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with only a few effective therapeutic options. A characteristic feature of PDAC is its unique tumor microenvironment (TME), termed desmoplasia, which shows extensive fibrosis and extracellular matrix deposition, generating highly hypoxic and nutrient-deprived conditions within the tumor. To thrive in this harsh TME, PDAC undergoes extensive metabolic rewiring that includes the altered use of glucose and glutamine, constitutive activation of autophagy-lysosomal pathways, and nutrient acquisition from host cells in the TME. Notably, these properties support PDAC metabolism and mediate therapeutic resistance, including immune suppression. A deeper understanding of the unique metabolic properties of PDAC and its TME may aid in the development of novel therapeutic strategies against this deadly disease.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497173PMC
http://dx.doi.org/10.3390/cancers14184351DOI Listing

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