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

ABSTRACT: 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.

SUBMITTER: Yamamoto K

PROVIDER: S-EPMC9497173 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Yamamoto Keisuke K Iwadate Dosuke D Kato Hiroyuki H Nakai Yousuke Y Tateishi Keisuke K Fujishiro Mitsuhiro M

Cancers 20220907 18

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 a ...[more]

PMID: 36139512

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