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Epigenetic Reprogramming for Targeting IDH-Mutant Malignant Gliomas

Targeting the epigenome has been considered a compelling treatment modality for several cancers, including gliomas. Nearly 80% of the lower-grade gliomas and secondary glioblastomas harbor recurrent mutations in isocitrate dehydrogenase (IDH). Mutant IDH generates high levels of 2-hydroxyglutarate (...

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Autores principales: Park, Jong-Whi, Turcan, Şevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826741/
https://www.ncbi.nlm.nih.gov/pubmed/31652645
http://dx.doi.org/10.3390/cancers11101616
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author Park, Jong-Whi
Turcan, Şevin
author_facet Park, Jong-Whi
Turcan, Şevin
author_sort Park, Jong-Whi
collection PubMed
description Targeting the epigenome has been considered a compelling treatment modality for several cancers, including gliomas. Nearly 80% of the lower-grade gliomas and secondary glioblastomas harbor recurrent mutations in isocitrate dehydrogenase (IDH). Mutant IDH generates high levels of 2-hydroxyglutarate (2-HG) that inhibit various components of the epigenetic machinery, including histone and DNA demethylases. The encouraging results from current epigenetic therapies in hematological malignancies have reinvigorated the interest in solid tumors and gliomas, both preclinically and clinically. Here, we summarize the recent advancements in epigenetic therapy for lower-grade gliomas and discuss the challenges associated with current treatment options. A particular focus is placed on therapeutic mechanisms underlying favorable outcome with epigenetic-based drugs in basic and translational research of gliomas. This review also highlights emerging bridges to combination treatment with respect to epigenetic drugs. Given that epigenetic therapies, particularly DNA methylation inhibitors, increase tumor immunogenicity and antitumor immune responses, appropriate drug combinations with immune checkpoint inhibitors may lead to improvement of treatment effectiveness of immunotherapy, ultimately leading to tumor cell eradication.
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spelling pubmed-68267412019-11-18 Epigenetic Reprogramming for Targeting IDH-Mutant Malignant Gliomas Park, Jong-Whi Turcan, Şevin Cancers (Basel) Review Targeting the epigenome has been considered a compelling treatment modality for several cancers, including gliomas. Nearly 80% of the lower-grade gliomas and secondary glioblastomas harbor recurrent mutations in isocitrate dehydrogenase (IDH). Mutant IDH generates high levels of 2-hydroxyglutarate (2-HG) that inhibit various components of the epigenetic machinery, including histone and DNA demethylases. The encouraging results from current epigenetic therapies in hematological malignancies have reinvigorated the interest in solid tumors and gliomas, both preclinically and clinically. Here, we summarize the recent advancements in epigenetic therapy for lower-grade gliomas and discuss the challenges associated with current treatment options. A particular focus is placed on therapeutic mechanisms underlying favorable outcome with epigenetic-based drugs in basic and translational research of gliomas. This review also highlights emerging bridges to combination treatment with respect to epigenetic drugs. Given that epigenetic therapies, particularly DNA methylation inhibitors, increase tumor immunogenicity and antitumor immune responses, appropriate drug combinations with immune checkpoint inhibitors may lead to improvement of treatment effectiveness of immunotherapy, ultimately leading to tumor cell eradication. MDPI 2019-10-22 /pmc/articles/PMC6826741/ /pubmed/31652645 http://dx.doi.org/10.3390/cancers11101616 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
Park, Jong-Whi
Turcan, Şevin
Epigenetic Reprogramming for Targeting IDH-Mutant Malignant Gliomas
title Epigenetic Reprogramming for Targeting IDH-Mutant Malignant Gliomas
title_full Epigenetic Reprogramming for Targeting IDH-Mutant Malignant Gliomas
title_fullStr Epigenetic Reprogramming for Targeting IDH-Mutant Malignant Gliomas
title_full_unstemmed Epigenetic Reprogramming for Targeting IDH-Mutant Malignant Gliomas
title_short Epigenetic Reprogramming for Targeting IDH-Mutant Malignant Gliomas
title_sort epigenetic reprogramming for targeting idh-mutant malignant gliomas
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826741/
https://www.ncbi.nlm.nih.gov/pubmed/31652645
http://dx.doi.org/10.3390/cancers11101616
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