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Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway
Treatment-resistance is common in glioblastoma (GBM) and the glioblastoma stem-like cells (GSC) from which they arise. Current treatment options are generally regarded as very poor and this arises from a poor conceptualization of the biological underpinnings of GBM/GSC and of the plasticity that the...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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OAE Publishing Inc.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992488/ https://www.ncbi.nlm.nih.gov/pubmed/35582450 http://dx.doi.org/10.20517/cdr.2020.17 |
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author | Anderson, George |
author_facet | Anderson, George |
author_sort | Anderson, George |
collection | PubMed |
description | Treatment-resistance is common in glioblastoma (GBM) and the glioblastoma stem-like cells (GSC) from which they arise. Current treatment options are generally regarded as very poor and this arises from a poor conceptualization of the biological underpinnings of GBM/GSC and of the plasticity that these cells are capable of utilizing in response to different treatments. A number of studies indicate melatonin to have utility in the management of GBM/GSC, both per se and when adjunctive to chemotherapy. Recent work shows melatonin to be produced in mitochondria, with the mitochondrial melatonergic pathway proposed to be a crucial factor in driving the wide array of changes in intra- and inter-cellular processes, as well as receptors that can be evident in the cells of the GBM/GSC microenvironment. Variations in the enzymatic conversion of N-acetylserotonin (NAS) to melatonin may be especially important in GSC, as NAS can activate the tyrosine receptor kinase B to increase GSC survival and proliferation. Consequently, variations in the NAS/melatonin ratio may have contrasting effects on GBM/GSC survival. It is proposed that mitochondrial communication across cell types in the tumour microenvironment is strongly driven by the need to carefully control the mitochondrial melatonergic pathways across cell types, with a number of intra- and inter-cellular processes occurring as a consequence of the need to carefully regulate the NAS/melatonin ratio. This better integrates previously disparate data on GBM/GSC as well as providing clear future research and treatment options. |
format | Online Article Text |
id | pubmed-8992488 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | OAE Publishing Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89924882022-05-16 Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway Anderson, George Cancer Drug Resist Review Treatment-resistance is common in glioblastoma (GBM) and the glioblastoma stem-like cells (GSC) from which they arise. Current treatment options are generally regarded as very poor and this arises from a poor conceptualization of the biological underpinnings of GBM/GSC and of the plasticity that these cells are capable of utilizing in response to different treatments. A number of studies indicate melatonin to have utility in the management of GBM/GSC, both per se and when adjunctive to chemotherapy. Recent work shows melatonin to be produced in mitochondria, with the mitochondrial melatonergic pathway proposed to be a crucial factor in driving the wide array of changes in intra- and inter-cellular processes, as well as receptors that can be evident in the cells of the GBM/GSC microenvironment. Variations in the enzymatic conversion of N-acetylserotonin (NAS) to melatonin may be especially important in GSC, as NAS can activate the tyrosine receptor kinase B to increase GSC survival and proliferation. Consequently, variations in the NAS/melatonin ratio may have contrasting effects on GBM/GSC survival. It is proposed that mitochondrial communication across cell types in the tumour microenvironment is strongly driven by the need to carefully control the mitochondrial melatonergic pathways across cell types, with a number of intra- and inter-cellular processes occurring as a consequence of the need to carefully regulate the NAS/melatonin ratio. This better integrates previously disparate data on GBM/GSC as well as providing clear future research and treatment options. OAE Publishing Inc. 2020-06-16 /pmc/articles/PMC8992488/ /pubmed/35582450 http://dx.doi.org/10.20517/cdr.2020.17 Text en © The Author(s) 2020. https://creativecommons.org/licenses/by/4.0/© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Anderson, George Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway |
title | Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway |
title_full | Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway |
title_fullStr | Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway |
title_full_unstemmed | Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway |
title_short | Glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway |
title_sort | glioblastoma chemoresistance: roles of the mitochondrial melatonergic pathway |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992488/ https://www.ncbi.nlm.nih.gov/pubmed/35582450 http://dx.doi.org/10.20517/cdr.2020.17 |
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