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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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.
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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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