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Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma

Glioblastoma WHO IV (GBM), the most common primary brain tumor in adults, is a heterogenous malignancy that displays a reprogrammed metabolism with various fuel sources at its disposal. Tumor cells primarily appear to consume glucose to entertain their anabolic and catabolic metabolism. While less e...

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Autores principales: Nguyen, Trang T. T., Shang, Enyuan, Westhoff, Mike-Andrew, Karpel-Massler, Georg, Siegelin, Markus D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563867/
https://www.ncbi.nlm.nih.gov/pubmed/36230918
http://dx.doi.org/10.3390/cells11192956
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author Nguyen, Trang T. T.
Shang, Enyuan
Westhoff, Mike-Andrew
Karpel-Massler, Georg
Siegelin, Markus D.
author_facet Nguyen, Trang T. T.
Shang, Enyuan
Westhoff, Mike-Andrew
Karpel-Massler, Georg
Siegelin, Markus D.
author_sort Nguyen, Trang T. T.
collection PubMed
description Glioblastoma WHO IV (GBM), the most common primary brain tumor in adults, is a heterogenous malignancy that displays a reprogrammed metabolism with various fuel sources at its disposal. Tumor cells primarily appear to consume glucose to entertain their anabolic and catabolic metabolism. While less effective for energy production, aerobic glycolysis (Warburg effect) is an effective means to drive biosynthesis of critical molecules required for relentless growth and resistance to cell death. Targeting the Warburg effect may be an effective venue for cancer treatment. However, past and recent evidence highlight that this approach may be limited in scope because GBM cells possess metabolic plasticity that allows them to harness other substrates, which include but are not limited to, fatty acids, amino acids, lactate, and acetate. Here, we review recent key findings in the literature that highlight that GBM cells substantially reprogram their metabolism upon therapy. These studies suggest that blocking glycolysis will yield a concomitant reactivation of oxidative energy pathways and most dominantly beta-oxidation of fatty acids.
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spelling pubmed-95638672022-10-15 Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma Nguyen, Trang T. T. Shang, Enyuan Westhoff, Mike-Andrew Karpel-Massler, Georg Siegelin, Markus D. Cells Review Glioblastoma WHO IV (GBM), the most common primary brain tumor in adults, is a heterogenous malignancy that displays a reprogrammed metabolism with various fuel sources at its disposal. Tumor cells primarily appear to consume glucose to entertain their anabolic and catabolic metabolism. While less effective for energy production, aerobic glycolysis (Warburg effect) is an effective means to drive biosynthesis of critical molecules required for relentless growth and resistance to cell death. Targeting the Warburg effect may be an effective venue for cancer treatment. However, past and recent evidence highlight that this approach may be limited in scope because GBM cells possess metabolic plasticity that allows them to harness other substrates, which include but are not limited to, fatty acids, amino acids, lactate, and acetate. Here, we review recent key findings in the literature that highlight that GBM cells substantially reprogram their metabolism upon therapy. These studies suggest that blocking glycolysis will yield a concomitant reactivation of oxidative energy pathways and most dominantly beta-oxidation of fatty acids. MDPI 2022-09-22 /pmc/articles/PMC9563867/ /pubmed/36230918 http://dx.doi.org/10.3390/cells11192956 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Nguyen, Trang T. T.
Shang, Enyuan
Westhoff, Mike-Andrew
Karpel-Massler, Georg
Siegelin, Markus D.
Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma
title Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma
title_full Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma
title_fullStr Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma
title_full_unstemmed Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma
title_short Therapeutic Drug-Induced Metabolic Reprogramming in Glioblastoma
title_sort therapeutic drug-induced metabolic reprogramming in glioblastoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563867/
https://www.ncbi.nlm.nih.gov/pubmed/36230918
http://dx.doi.org/10.3390/cells11192956
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