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High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas
Background: Meningiomas are the most common primary central nervous system tumors. 20–30% of these tumors are considered high-grade and associated with poor prognosis and high recurrence rates. Despite the high occurrence of meningiomas, there are no FDA-approved compounds for the treatment of these...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303324/ https://www.ncbi.nlm.nih.gov/pubmed/34300316 http://dx.doi.org/10.3390/jcm10143150 |
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author | Tatman, Philip D. Wroblewski, Tadeusz H. Fringuello, Anthony R. Scherer, Samuel R. Foreman, William B. Damek, Denise M. Lillehei, Kevin Youssef, A. Samy Jensen, Randy L. Graner, Michael W. Ormond, D. Ryan |
author_facet | Tatman, Philip D. Wroblewski, Tadeusz H. Fringuello, Anthony R. Scherer, Samuel R. Foreman, William B. Damek, Denise M. Lillehei, Kevin Youssef, A. Samy Jensen, Randy L. Graner, Michael W. Ormond, D. Ryan |
author_sort | Tatman, Philip D. |
collection | PubMed |
description | Background: Meningiomas are the most common primary central nervous system tumors. 20–30% of these tumors are considered high-grade and associated with poor prognosis and high recurrence rates. Despite the high occurrence of meningiomas, there are no FDA-approved compounds for the treatment of these tumors. Methods: In this study, we screened patient-cultured meningiomas with an epigenetic compound library to identify targetable mechanisms for the potential treatment of these tumors. Meningioma cell cultures were generated directly from surgically resected patient tumors and were cultured on a neural matrix. Cells were treated with a library of compounds meant to target epigenetic functions. Results: Although each tumor displayed a unique compound sensitivity profile, Panobinostat, LAQ824, and HC toxin were broadly effective across most tumors. These three compounds are broad-spectrum Histone Deacetylase (HDAC) inhibitors which target class I, IIa, and IIb HDACs. Panobinostat was identified as the most broadly effective compound, capable of significantly decreasing the average cell viability of the sample cohort, regardless of tumor grade, recurrence, radiation, and patient gender. Conclusions: These findings strongly suggest an important role of HDACs in meningioma biology and as a targetable mechanism. Additional validation studies are necessary to confirm these promising findings, as well to identify an ideal HDAC inhibitor candidate to develop for clinical use. |
format | Online Article Text |
id | pubmed-8303324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83033242021-07-25 High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas Tatman, Philip D. Wroblewski, Tadeusz H. Fringuello, Anthony R. Scherer, Samuel R. Foreman, William B. Damek, Denise M. Lillehei, Kevin Youssef, A. Samy Jensen, Randy L. Graner, Michael W. Ormond, D. Ryan J Clin Med Article Background: Meningiomas are the most common primary central nervous system tumors. 20–30% of these tumors are considered high-grade and associated with poor prognosis and high recurrence rates. Despite the high occurrence of meningiomas, there are no FDA-approved compounds for the treatment of these tumors. Methods: In this study, we screened patient-cultured meningiomas with an epigenetic compound library to identify targetable mechanisms for the potential treatment of these tumors. Meningioma cell cultures were generated directly from surgically resected patient tumors and were cultured on a neural matrix. Cells were treated with a library of compounds meant to target epigenetic functions. Results: Although each tumor displayed a unique compound sensitivity profile, Panobinostat, LAQ824, and HC toxin were broadly effective across most tumors. These three compounds are broad-spectrum Histone Deacetylase (HDAC) inhibitors which target class I, IIa, and IIb HDACs. Panobinostat was identified as the most broadly effective compound, capable of significantly decreasing the average cell viability of the sample cohort, regardless of tumor grade, recurrence, radiation, and patient gender. Conclusions: These findings strongly suggest an important role of HDACs in meningioma biology and as a targetable mechanism. Additional validation studies are necessary to confirm these promising findings, as well to identify an ideal HDAC inhibitor candidate to develop for clinical use. MDPI 2021-07-16 /pmc/articles/PMC8303324/ /pubmed/34300316 http://dx.doi.org/10.3390/jcm10143150 Text en © 2021 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 Tatman, Philip D. Wroblewski, Tadeusz H. Fringuello, Anthony R. Scherer, Samuel R. Foreman, William B. Damek, Denise M. Lillehei, Kevin Youssef, A. Samy Jensen, Randy L. Graner, Michael W. Ormond, D. Ryan High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas |
title | High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas |
title_full | High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas |
title_fullStr | High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas |
title_full_unstemmed | High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas |
title_short | High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas |
title_sort | high-throughput mechanistic screening of epigenetic compounds for the potential treatment of meningiomas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303324/ https://www.ncbi.nlm.nih.gov/pubmed/34300316 http://dx.doi.org/10.3390/jcm10143150 |
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