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Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research

Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment an...

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Autores principales: Caragher, Seamus, Chalmers, Anthony J., Gomez-Roman, Natividad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356812/
https://www.ncbi.nlm.nih.gov/pubmed/30621226
http://dx.doi.org/10.3390/cancers11010044
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author Caragher, Seamus
Chalmers, Anthony J.
Gomez-Roman, Natividad
author_facet Caragher, Seamus
Chalmers, Anthony J.
Gomez-Roman, Natividad
author_sort Caragher, Seamus
collection PubMed
description Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment.
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spelling pubmed-63568122019-02-05 Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research Caragher, Seamus Chalmers, Anthony J. Gomez-Roman, Natividad Cancers (Basel) Review Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment. MDPI 2019-01-04 /pmc/articles/PMC6356812/ /pubmed/30621226 http://dx.doi.org/10.3390/cancers11010044 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
Caragher, Seamus
Chalmers, Anthony J.
Gomez-Roman, Natividad
Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research
title Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research
title_full Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research
title_fullStr Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research
title_full_unstemmed Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research
title_short Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research
title_sort glioblastoma’s next top model: novel culture systems for brain cancer radiotherapy research
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356812/
https://www.ncbi.nlm.nih.gov/pubmed/30621226
http://dx.doi.org/10.3390/cancers11010044
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