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Drug target ranking for glioblastoma multiforme

BACKGROUND: Glioblastoma Multiforme, an aggressive primary brain tumor, has a poor prognosis and no effective standard of care treatments. Most patients undergoing radiotherapy, along with Temozolomide chemotherapy, develop resistance to the drug, and recurrence of the tumor is a common issue after...

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Autores principales: Saraf, Radhika, Agah, Shaghayegh, Datta, Aniruddha, Jiang, Xiaoqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074458/
https://www.ncbi.nlm.nih.gov/pubmed/33902757
http://dx.doi.org/10.1186/s42490-021-00052-w
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author Saraf, Radhika
Agah, Shaghayegh
Datta, Aniruddha
Jiang, Xiaoqian
author_facet Saraf, Radhika
Agah, Shaghayegh
Datta, Aniruddha
Jiang, Xiaoqian
author_sort Saraf, Radhika
collection PubMed
description BACKGROUND: Glioblastoma Multiforme, an aggressive primary brain tumor, has a poor prognosis and no effective standard of care treatments. Most patients undergoing radiotherapy, along with Temozolomide chemotherapy, develop resistance to the drug, and recurrence of the tumor is a common issue after the treatment. We propose to model the pathways active in Glioblastoma using Boolean network techniques. The network captures the genetic interactions and possible mutations that are involved in the development of the brain tumor. The model is used to predict the theoretical efficacies of drugs for the treatment of cancer. RESULTS: We use the Boolean network to rank the critical intervention points in the pathway to predict an effective therapeutic strategy for Glioblastoma. Drug repurposing helps to identify non-cancer drugs that could be effective in cancer treatment. We predict the effectiveness of drug combinations of anti-cancer and non-cancer drugs for Glioblastoma. CONCLUSIONS: Given the genetic profile of a GBM tumor, the Boolean model can predict the most effective targets for treatment. We also identified two-drug combinations that could be more effective in killing GBM cells than conventional chemotherapeutic agents. The non-cancer drug Aspirin could potentially increase the cytotoxicity of TMZ in GBM patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s42490-021-00052-w).
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spelling pubmed-80744582021-04-29 Drug target ranking for glioblastoma multiforme Saraf, Radhika Agah, Shaghayegh Datta, Aniruddha Jiang, Xiaoqian BMC Biomed Eng Research Article BACKGROUND: Glioblastoma Multiforme, an aggressive primary brain tumor, has a poor prognosis and no effective standard of care treatments. Most patients undergoing radiotherapy, along with Temozolomide chemotherapy, develop resistance to the drug, and recurrence of the tumor is a common issue after the treatment. We propose to model the pathways active in Glioblastoma using Boolean network techniques. The network captures the genetic interactions and possible mutations that are involved in the development of the brain tumor. The model is used to predict the theoretical efficacies of drugs for the treatment of cancer. RESULTS: We use the Boolean network to rank the critical intervention points in the pathway to predict an effective therapeutic strategy for Glioblastoma. Drug repurposing helps to identify non-cancer drugs that could be effective in cancer treatment. We predict the effectiveness of drug combinations of anti-cancer and non-cancer drugs for Glioblastoma. CONCLUSIONS: Given the genetic profile of a GBM tumor, the Boolean model can predict the most effective targets for treatment. We also identified two-drug combinations that could be more effective in killing GBM cells than conventional chemotherapeutic agents. The non-cancer drug Aspirin could potentially increase the cytotoxicity of TMZ in GBM patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s42490-021-00052-w). BioMed Central 2021-04-26 /pmc/articles/PMC8074458/ /pubmed/33902757 http://dx.doi.org/10.1186/s42490-021-00052-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Saraf, Radhika
Agah, Shaghayegh
Datta, Aniruddha
Jiang, Xiaoqian
Drug target ranking for glioblastoma multiforme
title Drug target ranking for glioblastoma multiforme
title_full Drug target ranking for glioblastoma multiforme
title_fullStr Drug target ranking for glioblastoma multiforme
title_full_unstemmed Drug target ranking for glioblastoma multiforme
title_short Drug target ranking for glioblastoma multiforme
title_sort drug target ranking for glioblastoma multiforme
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074458/
https://www.ncbi.nlm.nih.gov/pubmed/33902757
http://dx.doi.org/10.1186/s42490-021-00052-w
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