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Targeting cancer cell metabolism in pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplas...

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Autores principales: Cohen, Romain, Neuzillet, Cindy, Tijeras-Raballand, Annemilaï, Faivre, Sandrine, de Gramont, Armand, Raymond, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627277/
https://www.ncbi.nlm.nih.gov/pubmed/26164081
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author Cohen, Romain
Neuzillet, Cindy
Tijeras-Raballand, Annemilaï
Faivre, Sandrine
de Gramont, Armand
Raymond, Eric
author_facet Cohen, Romain
Neuzillet, Cindy
Tijeras-Raballand, Annemilaï
Faivre, Sandrine
de Gramont, Armand
Raymond, Eric
author_sort Cohen, Romain
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic reprogramming to the forefront of PDAC therapeutic research. The Warburg effect, glutamine addiction, and autophagy stand as the most important adaptive metabolic mechanisms of cancer cells themselves, however metabolic reprogramming is also an important feature of the tumor microenvironment, having a major impact on epigenetic reprogramming and tumor cell interactions with its complex stroma. We present a comprehensive overview of the main metabolic adaptations contributing to PDAC development and progression. A review of current and future therapies targeting this range of metabolic pathways is provided.
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spelling pubmed-46272772015-12-02 Targeting cancer cell metabolism in pancreatic adenocarcinoma Cohen, Romain Neuzillet, Cindy Tijeras-Raballand, Annemilaï Faivre, Sandrine de Gramont, Armand Raymond, Eric Oncotarget Review Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic reprogramming to the forefront of PDAC therapeutic research. The Warburg effect, glutamine addiction, and autophagy stand as the most important adaptive metabolic mechanisms of cancer cells themselves, however metabolic reprogramming is also an important feature of the tumor microenvironment, having a major impact on epigenetic reprogramming and tumor cell interactions with its complex stroma. We present a comprehensive overview of the main metabolic adaptations contributing to PDAC development and progression. A review of current and future therapies targeting this range of metabolic pathways is provided. Impact Journals LLC 2015-06-10 /pmc/articles/PMC4627277/ /pubmed/26164081 Text en Copyright: © 2015 Cohen et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Review
Cohen, Romain
Neuzillet, Cindy
Tijeras-Raballand, Annemilaï
Faivre, Sandrine
de Gramont, Armand
Raymond, Eric
Targeting cancer cell metabolism in pancreatic adenocarcinoma
title Targeting cancer cell metabolism in pancreatic adenocarcinoma
title_full Targeting cancer cell metabolism in pancreatic adenocarcinoma
title_fullStr Targeting cancer cell metabolism in pancreatic adenocarcinoma
title_full_unstemmed Targeting cancer cell metabolism in pancreatic adenocarcinoma
title_short Targeting cancer cell metabolism in pancreatic adenocarcinoma
title_sort targeting cancer cell metabolism in pancreatic adenocarcinoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627277/
https://www.ncbi.nlm.nih.gov/pubmed/26164081
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