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Advances in epigenetic glioblastoma therapy

View Article: PubMed Central - PubMed

ABSTRACT

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults despite contemporary gold-standard first-line treatment strategies. This type of tumor recurs in virtually all patients and no commonly accepted standard treatment exists for the recurrent disease. Therefore, advances in all scientific and clinical aspects of GBM are urgently needed. Epigenetic mechanisms are one of the major factors contributing to the pathogenesis of cancers, including glioblastoma. Epigenetic modulators that regulate gene expression by altering the epigenome and non-histone proteins are being exploited as therapeutic drug targets. Over the last decade, numerous preclinical and clinical studies on histone deacetylase (HDAC) inhibitors have shown promising results in various cancers. This article provides an overview of the anticancer mechanisms of HDAC inhibitors and the role of HDAC isoforms in GBM. We also summarize current knowledge on HDAC inhibitors on the basis of preclinical studies and emerging clinical data.

No MeSH data available.


Antitumoral activity of HDAC inhibitors
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Figure 1: Antitumoral activity of HDAC inhibitors

Mentions: HDAC inhibitors are classified as epigenetic agents that target the aberrant epigenetic characteristics of tumor cells. Epigenetic alterations modulate cellular phenotype through changes in gene expression without modifying the DNA sequence [19]. HDAC inhibitors are known as effective therapeutic anticancer agents via multiple mechanisms, including the induction of cell-cycle arrest, differentiation, senescence, intrinsic and extrinsic apoptosis, mitotic cell death, autophagic cell death, generation of reactive oxygen species, inhibition of angiogenesis and metastasis, and improvement in tumor immunity [8, 51] (Table 1 and Figure 1). Because these diverse effects on cancer cells overlap, HDAC inhibitors are very attractive as single agents and in combination with other therapies (Table 2). HDAC inhibitors are a promising class of therapeutic agents that are under investigation for treating different types of tumors, including GBM.


Advances in epigenetic glioblastoma therapy
Antitumoral activity of HDAC inhibitors
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392350&req=5

Figure 1: Antitumoral activity of HDAC inhibitors
Mentions: HDAC inhibitors are classified as epigenetic agents that target the aberrant epigenetic characteristics of tumor cells. Epigenetic alterations modulate cellular phenotype through changes in gene expression without modifying the DNA sequence [19]. HDAC inhibitors are known as effective therapeutic anticancer agents via multiple mechanisms, including the induction of cell-cycle arrest, differentiation, senescence, intrinsic and extrinsic apoptosis, mitotic cell death, autophagic cell death, generation of reactive oxygen species, inhibition of angiogenesis and metastasis, and improvement in tumor immunity [8, 51] (Table 1 and Figure 1). Because these diverse effects on cancer cells overlap, HDAC inhibitors are very attractive as single agents and in combination with other therapies (Table 2). HDAC inhibitors are a promising class of therapeutic agents that are under investigation for treating different types of tumors, including GBM.

View Article: PubMed Central - PubMed

ABSTRACT

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults despite contemporary gold-standard first-line treatment strategies. This type of tumor recurs in virtually all patients and no commonly accepted standard treatment exists for the recurrent disease. Therefore, advances in all scientific and clinical aspects of GBM are urgently needed. Epigenetic mechanisms are one of the major factors contributing to the pathogenesis of cancers, including glioblastoma. Epigenetic modulators that regulate gene expression by altering the epigenome and non-histone proteins are being exploited as therapeutic drug targets. Over the last decade, numerous preclinical and clinical studies on histone deacetylase (HDAC) inhibitors have shown promising results in various cancers. This article provides an overview of the anticancer mechanisms of HDAC inhibitors and the role of HDAC isoforms in GBM. We also summarize current knowledge on HDAC inhibitors on the basis of preclinical studies and emerging clinical data.

No MeSH data available.