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Temozolomide and Other Alkylating Agents in Glioblastoma Therapy
The alkylating agent temozolomide (TMZ) together with maximal safe bulk resection and focal radiotherapy comprises the standard treatment for glioblastoma (GB), a particularly aggressive and lethal primary brain tumor. GB affects 3.2 in 100,000 people who have an average survival time of around 14 m...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783999/ https://www.ncbi.nlm.nih.gov/pubmed/31505812 http://dx.doi.org/10.3390/biomedicines7030069 |
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author | Strobel, Hannah Baisch, Tim Fitzel, Rahel Schilberg, Katharina Siegelin, Markus D. Karpel-Massler, Georg Debatin, Klaus-Michael Westhoff, Mike-Andrew |
author_facet | Strobel, Hannah Baisch, Tim Fitzel, Rahel Schilberg, Katharina Siegelin, Markus D. Karpel-Massler, Georg Debatin, Klaus-Michael Westhoff, Mike-Andrew |
author_sort | Strobel, Hannah |
collection | PubMed |
description | The alkylating agent temozolomide (TMZ) together with maximal safe bulk resection and focal radiotherapy comprises the standard treatment for glioblastoma (GB), a particularly aggressive and lethal primary brain tumor. GB affects 3.2 in 100,000 people who have an average survival time of around 14 months after presentation. Several key aspects make GB a difficult to treat disease, primarily including the high resistance of tumor cells to cell death-inducing substances or radiation and the combination of the highly invasive nature of the malignancy, i.e., treatment must affect the whole brain, and the protection from drugs of the tumor bulk—or at least of the invading cells—by the blood brain barrier (BBB). TMZ crosses the BBB, but—unlike classic chemotherapeutics—does not induce DNA damage or misalignment of segregating chromosomes directly. It has been described as a DNA alkylating agent, which leads to base mismatches that initiate futile DNA repair cycles; eventually, DNA strand breaks, which in turn induces cell death. However, while much is assumed about the function of TMZ and its mode of action, primary data are actually scarce and often contradictory. To improve GB treatment further, we need to fully understand what TMZ does to the tumor cells and their microenvironment. This is of particular importance, as novel therapeutic approaches are almost always clinically assessed in the presence of standard treatment, i.e., in the presence of TMZ. Therefore, potential pharmacological interactions between TMZ and novel drugs might occur with unforeseeable consequences. |
format | Online Article Text |
id | pubmed-6783999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67839992019-10-16 Temozolomide and Other Alkylating Agents in Glioblastoma Therapy Strobel, Hannah Baisch, Tim Fitzel, Rahel Schilberg, Katharina Siegelin, Markus D. Karpel-Massler, Georg Debatin, Klaus-Michael Westhoff, Mike-Andrew Biomedicines Review The alkylating agent temozolomide (TMZ) together with maximal safe bulk resection and focal radiotherapy comprises the standard treatment for glioblastoma (GB), a particularly aggressive and lethal primary brain tumor. GB affects 3.2 in 100,000 people who have an average survival time of around 14 months after presentation. Several key aspects make GB a difficult to treat disease, primarily including the high resistance of tumor cells to cell death-inducing substances or radiation and the combination of the highly invasive nature of the malignancy, i.e., treatment must affect the whole brain, and the protection from drugs of the tumor bulk—or at least of the invading cells—by the blood brain barrier (BBB). TMZ crosses the BBB, but—unlike classic chemotherapeutics—does not induce DNA damage or misalignment of segregating chromosomes directly. It has been described as a DNA alkylating agent, which leads to base mismatches that initiate futile DNA repair cycles; eventually, DNA strand breaks, which in turn induces cell death. However, while much is assumed about the function of TMZ and its mode of action, primary data are actually scarce and often contradictory. To improve GB treatment further, we need to fully understand what TMZ does to the tumor cells and their microenvironment. This is of particular importance, as novel therapeutic approaches are almost always clinically assessed in the presence of standard treatment, i.e., in the presence of TMZ. Therefore, potential pharmacological interactions between TMZ and novel drugs might occur with unforeseeable consequences. MDPI 2019-09-09 /pmc/articles/PMC6783999/ /pubmed/31505812 http://dx.doi.org/10.3390/biomedicines7030069 Text en © 2019 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 Strobel, Hannah Baisch, Tim Fitzel, Rahel Schilberg, Katharina Siegelin, Markus D. Karpel-Massler, Georg Debatin, Klaus-Michael Westhoff, Mike-Andrew Temozolomide and Other Alkylating Agents in Glioblastoma Therapy |
title | Temozolomide and Other Alkylating Agents in Glioblastoma Therapy |
title_full | Temozolomide and Other Alkylating Agents in Glioblastoma Therapy |
title_fullStr | Temozolomide and Other Alkylating Agents in Glioblastoma Therapy |
title_full_unstemmed | Temozolomide and Other Alkylating Agents in Glioblastoma Therapy |
title_short | Temozolomide and Other Alkylating Agents in Glioblastoma Therapy |
title_sort | temozolomide and other alkylating agents in glioblastoma therapy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783999/ https://www.ncbi.nlm.nih.gov/pubmed/31505812 http://dx.doi.org/10.3390/biomedicines7030069 |
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