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The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor

There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat...

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Autores principales: Valvona, Cara J., Fillmore, Helen L., Nunn, Peter B., Pilkington, Geoffrey J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029296/
https://www.ncbi.nlm.nih.gov/pubmed/26269128
http://dx.doi.org/10.1111/bpa.12299
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author Valvona, Cara J.
Fillmore, Helen L.
Nunn, Peter B.
Pilkington, Geoffrey J.
author_facet Valvona, Cara J.
Fillmore, Helen L.
Nunn, Peter B.
Pilkington, Geoffrey J.
author_sort Valvona, Cara J.
collection PubMed
description There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat primary brain tumors and patient survival remains poor. Tumor metabolism is important to consider in therapeutic approaches and is the focus of numerous research investigations. Lactate dehydrogenase A (LDHA) is a cytosolic enzyme, predominantly involved in anaerobic and aerobic glycolysis (the Warburg effect); however, it has multiple additional functions in non‐neoplastic and neoplastic tissues, which are not commonly known or discussed. This review summarizes what is currently known about the function of LDHA and identifies areas that would benefit from further exploration. The current knowledge of the role of LDHA in the brain and its potential as a therapeutic target for brain tumors will also be highlighted. The Warburg effect appears to be universal in tumors, including primary brain tumors, and LDHA (because of its involvement with this process) has been identified as a potential therapeutic target. Currently, there are, however, no suitable LDHA inhibitors available for tumor therapies in the clinic.
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spelling pubmed-80292962021-09-03 The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor Valvona, Cara J. Fillmore, Helen L. Nunn, Peter B. Pilkington, Geoffrey J. Brain Pathol Review There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat primary brain tumors and patient survival remains poor. Tumor metabolism is important to consider in therapeutic approaches and is the focus of numerous research investigations. Lactate dehydrogenase A (LDHA) is a cytosolic enzyme, predominantly involved in anaerobic and aerobic glycolysis (the Warburg effect); however, it has multiple additional functions in non‐neoplastic and neoplastic tissues, which are not commonly known or discussed. This review summarizes what is currently known about the function of LDHA and identifies areas that would benefit from further exploration. The current knowledge of the role of LDHA in the brain and its potential as a therapeutic target for brain tumors will also be highlighted. The Warburg effect appears to be universal in tumors, including primary brain tumors, and LDHA (because of its involvement with this process) has been identified as a potential therapeutic target. Currently, there are, however, no suitable LDHA inhibitors available for tumor therapies in the clinic. John Wiley and Sons Inc. 2015-09-17 /pmc/articles/PMC8029296/ /pubmed/26269128 http://dx.doi.org/10.1111/bpa.12299 Text en © 2015 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Valvona, Cara J.
Fillmore, Helen L.
Nunn, Peter B.
Pilkington, Geoffrey J.
The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor
title The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor
title_full The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor
title_fullStr The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor
title_full_unstemmed The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor
title_short The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor
title_sort regulation and function of lactate dehydrogenase a: therapeutic potential in brain tumor
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029296/
https://www.ncbi.nlm.nih.gov/pubmed/26269128
http://dx.doi.org/10.1111/bpa.12299
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