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Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma
Drug resistance limits the therapeutic efficacy in cancers and leads to tumor recurrence through ill-defined mechanisms. Glioblastoma (GBM) are the deadliest brain tumors in adults. GBM, at diagnosis or after treatment, are resistant to temozolomide (TMZ), the standard chemotherapy. To better unders...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944699/ https://www.ncbi.nlm.nih.gov/pubmed/31907355 http://dx.doi.org/10.1038/s41419-019-2200-2 |
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author | Rabé, Marion Dumont, Solenne Álvarez-Arenas, Arturo Janati, Hicham Belmonte-Beitia, Juan Calvo, Gabriel F. Thibault-Carpentier, Christelle Séry, Quentin Chauvin, Cynthia Joalland, Noémie Briand, Floriane Blandin, Stéphanie Scotet, Emmanuel Pecqueur, Claire Clairambault, Jean Oliver, Lisa Perez-Garcia, Victor Nadaradjane, Arulraj Cartron, Pierre-François Gratas, Catherine Vallette, François M. |
author_facet | Rabé, Marion Dumont, Solenne Álvarez-Arenas, Arturo Janati, Hicham Belmonte-Beitia, Juan Calvo, Gabriel F. Thibault-Carpentier, Christelle Séry, Quentin Chauvin, Cynthia Joalland, Noémie Briand, Floriane Blandin, Stéphanie Scotet, Emmanuel Pecqueur, Claire Clairambault, Jean Oliver, Lisa Perez-Garcia, Victor Nadaradjane, Arulraj Cartron, Pierre-François Gratas, Catherine Vallette, François M. |
author_sort | Rabé, Marion |
collection | PubMed |
description | Drug resistance limits the therapeutic efficacy in cancers and leads to tumor recurrence through ill-defined mechanisms. Glioblastoma (GBM) are the deadliest brain tumors in adults. GBM, at diagnosis or after treatment, are resistant to temozolomide (TMZ), the standard chemotherapy. To better understand the acquisition of this resistance, we performed a longitudinal study, using a combination of mathematical models, RNA sequencing, single cell analyses, functional and drug assays in a human glioma cell line (U251). After an initial response characterized by cell death induction, cells entered a transient state defined by slow growth, a distinct morphology and a shift of metabolism. Specific genes expression associated to this population revealed chromatin remodeling. Indeed, the histone deacetylase inhibitor trichostatin (TSA), specifically eliminated this population and thus prevented the appearance of fast growing TMZ-resistant cells. In conclusion, we have identified in glioblastoma a population with tolerant-like features, which could constitute a therapeutic target. |
format | Online Article Text |
id | pubmed-6944699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69446992020-01-07 Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma Rabé, Marion Dumont, Solenne Álvarez-Arenas, Arturo Janati, Hicham Belmonte-Beitia, Juan Calvo, Gabriel F. Thibault-Carpentier, Christelle Séry, Quentin Chauvin, Cynthia Joalland, Noémie Briand, Floriane Blandin, Stéphanie Scotet, Emmanuel Pecqueur, Claire Clairambault, Jean Oliver, Lisa Perez-Garcia, Victor Nadaradjane, Arulraj Cartron, Pierre-François Gratas, Catherine Vallette, François M. Cell Death Dis Article Drug resistance limits the therapeutic efficacy in cancers and leads to tumor recurrence through ill-defined mechanisms. Glioblastoma (GBM) are the deadliest brain tumors in adults. GBM, at diagnosis or after treatment, are resistant to temozolomide (TMZ), the standard chemotherapy. To better understand the acquisition of this resistance, we performed a longitudinal study, using a combination of mathematical models, RNA sequencing, single cell analyses, functional and drug assays in a human glioma cell line (U251). After an initial response characterized by cell death induction, cells entered a transient state defined by slow growth, a distinct morphology and a shift of metabolism. Specific genes expression associated to this population revealed chromatin remodeling. Indeed, the histone deacetylase inhibitor trichostatin (TSA), specifically eliminated this population and thus prevented the appearance of fast growing TMZ-resistant cells. In conclusion, we have identified in glioblastoma a population with tolerant-like features, which could constitute a therapeutic target. Nature Publishing Group UK 2020-01-06 /pmc/articles/PMC6944699/ /pubmed/31907355 http://dx.doi.org/10.1038/s41419-019-2200-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Rabé, Marion Dumont, Solenne Álvarez-Arenas, Arturo Janati, Hicham Belmonte-Beitia, Juan Calvo, Gabriel F. Thibault-Carpentier, Christelle Séry, Quentin Chauvin, Cynthia Joalland, Noémie Briand, Floriane Blandin, Stéphanie Scotet, Emmanuel Pecqueur, Claire Clairambault, Jean Oliver, Lisa Perez-Garcia, Victor Nadaradjane, Arulraj Cartron, Pierre-François Gratas, Catherine Vallette, François M. Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma |
title | Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma |
title_full | Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma |
title_fullStr | Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma |
title_full_unstemmed | Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma |
title_short | Identification of a transient state during the acquisition of temozolomide resistance in glioblastoma |
title_sort | identification of a transient state during the acquisition of temozolomide resistance in glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944699/ https://www.ncbi.nlm.nih.gov/pubmed/31907355 http://dx.doi.org/10.1038/s41419-019-2200-2 |
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