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Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality

Glioblastoma multiforme (GBM) represents approximately 60% of all brain tumors in adults. This malignancy shows a high biological and genetic heterogeneity associated with exceptional aggressiveness, leading to a poor survival of patients. This review provides a summary of the basic biology of GBM c...

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Autores principales: Vitovcova, Barbora, Skarkova, Veronika, Rudolf, Kamil, Rudolf, Emil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432846/
https://www.ncbi.nlm.nih.gov/pubmed/32727112
http://dx.doi.org/10.3390/ijms21155324
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author Vitovcova, Barbora
Skarkova, Veronika
Rudolf, Kamil
Rudolf, Emil
author_facet Vitovcova, Barbora
Skarkova, Veronika
Rudolf, Kamil
Rudolf, Emil
author_sort Vitovcova, Barbora
collection PubMed
description Glioblastoma multiforme (GBM) represents approximately 60% of all brain tumors in adults. This malignancy shows a high biological and genetic heterogeneity associated with exceptional aggressiveness, leading to a poor survival of patients. This review provides a summary of the basic biology of GBM cells with emphasis on cell cycle and cytoskeletal apparatus of these cells, in particular microtubules. Their involvement in the important oncosuppressive process called mitotic catastrophe will next be discussed along with select examples of microtubule-targeting agents, which are currently explored in this respect such as benzimidazole carbamate compounds. Select microtubule-targeting agents, in particular benzimidazole carbamates, induce G(2)/M cell cycle arrest and mitotic catastrophe in tumor cells including GBM, resulting in phenotypically variable cell fates such as mitotic death or mitotic slippage with subsequent cell demise or permanent arrest leading to senescence. Their effect is coupled with low toxicity in normal cells and not developed chemoresistance. Given the lack of efficient cytostatics or modern molecular target-specific compounds in the treatment of GBM, drugs inducing mitotic catastrophe might offer a new, efficient alternative to the existing clinical management of this at present incurable malignancy.
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spelling pubmed-74328462020-08-27 Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality Vitovcova, Barbora Skarkova, Veronika Rudolf, Kamil Rudolf, Emil Int J Mol Sci Review Glioblastoma multiforme (GBM) represents approximately 60% of all brain tumors in adults. This malignancy shows a high biological and genetic heterogeneity associated with exceptional aggressiveness, leading to a poor survival of patients. This review provides a summary of the basic biology of GBM cells with emphasis on cell cycle and cytoskeletal apparatus of these cells, in particular microtubules. Their involvement in the important oncosuppressive process called mitotic catastrophe will next be discussed along with select examples of microtubule-targeting agents, which are currently explored in this respect such as benzimidazole carbamate compounds. Select microtubule-targeting agents, in particular benzimidazole carbamates, induce G(2)/M cell cycle arrest and mitotic catastrophe in tumor cells including GBM, resulting in phenotypically variable cell fates such as mitotic death or mitotic slippage with subsequent cell demise or permanent arrest leading to senescence. Their effect is coupled with low toxicity in normal cells and not developed chemoresistance. Given the lack of efficient cytostatics or modern molecular target-specific compounds in the treatment of GBM, drugs inducing mitotic catastrophe might offer a new, efficient alternative to the existing clinical management of this at present incurable malignancy. MDPI 2020-07-27 /pmc/articles/PMC7432846/ /pubmed/32727112 http://dx.doi.org/10.3390/ijms21155324 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Vitovcova, Barbora
Skarkova, Veronika
Rudolf, Kamil
Rudolf, Emil
Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality
title Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality
title_full Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality
title_fullStr Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality
title_full_unstemmed Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality
title_short Biology of Glioblastoma Multiforme—Exploration of Mitotic Catastrophe as a Potential Treatment Modality
title_sort biology of glioblastoma multiforme—exploration of mitotic catastrophe as a potential treatment modality
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432846/
https://www.ncbi.nlm.nih.gov/pubmed/32727112
http://dx.doi.org/10.3390/ijms21155324
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