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Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas

Tumor Treating Fields (TTFields) were incorporated into the treatment of glioblastoma, the most malignant brain tumor, after showing an effect on progression-free and overall survival in a phase III clinical trial. The combination of TTFields and an antimitotic drug might further improve this approa...

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Autores principales: Krex, Dietmar, Bartmann, Paula, Lachmann, Doris, Hagstotz, Alexander, Jugel, Willi, Schneiderman, Rosa S., Gotlib, Karnit, Porat, Yaara, Robel, Katja, Temme, Achim, Giladi, Moshe, Michen, Susanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003311/
https://www.ncbi.nlm.nih.gov/pubmed/36902447
http://dx.doi.org/10.3390/ijms24055016
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author Krex, Dietmar
Bartmann, Paula
Lachmann, Doris
Hagstotz, Alexander
Jugel, Willi
Schneiderman, Rosa S.
Gotlib, Karnit
Porat, Yaara
Robel, Katja
Temme, Achim
Giladi, Moshe
Michen, Susanne
author_facet Krex, Dietmar
Bartmann, Paula
Lachmann, Doris
Hagstotz, Alexander
Jugel, Willi
Schneiderman, Rosa S.
Gotlib, Karnit
Porat, Yaara
Robel, Katja
Temme, Achim
Giladi, Moshe
Michen, Susanne
author_sort Krex, Dietmar
collection PubMed
description Tumor Treating Fields (TTFields) were incorporated into the treatment of glioblastoma, the most malignant brain tumor, after showing an effect on progression-free and overall survival in a phase III clinical trial. The combination of TTFields and an antimitotic drug might further improve this approach. Here, we tested the combination of TTFields with AZD1152, an Aurora B kinase inhibitor, in primary cultures of newly diagnosed (ndGBM) and recurrent glioblastoma (rGBM). AZD1152 concentration was titrated for each cell line and 5–30 nM were used alone or in addition to TTFields (1.6 V/cm RMS; 200 kHz) applied for 72 h using the inovitro™ system. Cell morphological changes were visualized by conventional and confocal laser microscopy. The cytotoxic effects were determined by cell viability assays. Primary cultures of ndGBM and rGBM varied in p53 mutational status; ploidy; EGFR expression and MGMT-promoter methylation status. Nevertheless; in all primary cultures; a significant cytotoxic effect was found following TTFields treatment alone and in all but one, a significant effect after treatment with AZD1152 alone was also observed. Moreover, in all primary cultures the combined treatment had the most pronounced cytotoxic effect in parallel with morphological changes. The combined treatment of TTFields and AZD1152 led to a significant reduction in the number of ndGBM and rGBM cells compared to each treatment alone. Further evaluation of this approach, which has to be considered as a proof of concept, is warranted, before entering into early clinical trials.
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spelling pubmed-100033112023-03-11 Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas Krex, Dietmar Bartmann, Paula Lachmann, Doris Hagstotz, Alexander Jugel, Willi Schneiderman, Rosa S. Gotlib, Karnit Porat, Yaara Robel, Katja Temme, Achim Giladi, Moshe Michen, Susanne Int J Mol Sci Article Tumor Treating Fields (TTFields) were incorporated into the treatment of glioblastoma, the most malignant brain tumor, after showing an effect on progression-free and overall survival in a phase III clinical trial. The combination of TTFields and an antimitotic drug might further improve this approach. Here, we tested the combination of TTFields with AZD1152, an Aurora B kinase inhibitor, in primary cultures of newly diagnosed (ndGBM) and recurrent glioblastoma (rGBM). AZD1152 concentration was titrated for each cell line and 5–30 nM were used alone or in addition to TTFields (1.6 V/cm RMS; 200 kHz) applied for 72 h using the inovitro™ system. Cell morphological changes were visualized by conventional and confocal laser microscopy. The cytotoxic effects were determined by cell viability assays. Primary cultures of ndGBM and rGBM varied in p53 mutational status; ploidy; EGFR expression and MGMT-promoter methylation status. Nevertheless; in all primary cultures; a significant cytotoxic effect was found following TTFields treatment alone and in all but one, a significant effect after treatment with AZD1152 alone was also observed. Moreover, in all primary cultures the combined treatment had the most pronounced cytotoxic effect in parallel with morphological changes. The combined treatment of TTFields and AZD1152 led to a significant reduction in the number of ndGBM and rGBM cells compared to each treatment alone. Further evaluation of this approach, which has to be considered as a proof of concept, is warranted, before entering into early clinical trials. MDPI 2023-03-06 /pmc/articles/PMC10003311/ /pubmed/36902447 http://dx.doi.org/10.3390/ijms24055016 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krex, Dietmar
Bartmann, Paula
Lachmann, Doris
Hagstotz, Alexander
Jugel, Willi
Schneiderman, Rosa S.
Gotlib, Karnit
Porat, Yaara
Robel, Katja
Temme, Achim
Giladi, Moshe
Michen, Susanne
Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas
title Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas
title_full Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas
title_fullStr Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas
title_full_unstemmed Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas
title_short Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas
title_sort aurora b kinase inhibition by azd1152 concomitant with tumor treating fields is effective in the treatment of cultures from primary and recurrent glioblastomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003311/
https://www.ncbi.nlm.nih.gov/pubmed/36902447
http://dx.doi.org/10.3390/ijms24055016
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