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Profile of belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma.

Bodiford A, Bodge M, Talbott MS, Reddy NM - Onco Targets Ther (2014)

Bottom Line: There is an urgent need to optimize induction therapy by incorporating novel agents that target the dysregulated pathways.Histone deacetylase inhibitors that induce acetylation of histones and enhance apoptosis have shown promising activity.In this article, we summarize the role of histone deacetylase inhibitors and specifically discuss pharmacokinetics, efficacy, and toxicity of the recently US Food and Drug Administration-approved agent belinostat for its use in patients with relapsed/refractory peripheral T-cell lymphoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA.

ABSTRACT
The peripheral T-cell lymphomas are a rare and heterogeneous group of mature T-cell lymphomas with limited available therapies. The outcome of frontline chemotherapy regimens has been disappointing, with a long-term survival of only 20%-30%. There is an urgent need to optimize induction therapy by incorporating novel agents that target the dysregulated pathways. Histone deacetylase inhibitors that induce acetylation of histones and enhance apoptosis have shown promising activity. In this article, we summarize the role of histone deacetylase inhibitors and specifically discuss pharmacokinetics, efficacy, and toxicity of the recently US Food and Drug Administration-approved agent belinostat for its use in patients with relapsed/refractory peripheral T-cell lymphoma.

No MeSH data available.


Related in: MedlinePlus

Pharmacology of histone deacetylase (HDAC) inhibitors.Note: Belinostat allows hyperacetylation of suppressed genes, resulting in cell growth and/or apoptosis in malignant cells.
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f1-ott-7-1971: Pharmacology of histone deacetylase (HDAC) inhibitors.Note: Belinostat allows hyperacetylation of suppressed genes, resulting in cell growth and/or apoptosis in malignant cells.

Mentions: HDACi play a crucial role in the acetylation and deacetylation of histones and exert their action through removing acetyl groups from histones. The deacetylation of histones results in a more condensed chromatin structure, which causes transcriptional deactivation. Transcriptional deactivation allows undifferentiated growth and cell proliferation (Figure 1). Chromatin is found in the nucleus of many eukaryotic cells and is composed of DNA and proteins. A major function of chromatin is to protect DNA from damage. Histones are a major protein that comprise chromatin, and there has been increased interest over the past decade in the aberrant process of histone modifications, specifically histone acetylation. Levels of acetylation are balanced by histone acetyl-transferase and HDAC, and this balance plays a role in gene transcription/regulation as well as DNA repair. HDAC exerts its activity by removing acetyl groups from lysine located on histones, causing a more compact chromatin. This formation causes transcriptional gene silencing, resulting in increased potential for unregulated cell proliferation. There are approximately 18 different HDACs categorized into four classes, where HDACi inhibit class I and II. Class I HDACs regulate cell proliferation, while class II suppress apoptosis in malignant cells.14 Through this inhibition, HDACi exert its antineoplastic activity by allowing hyperacetylation of suppressed genes, resulting in cell growth arrest and/or apoptosis in malignant cells.15 A more comprehensive explanation of this mechanism of action has been described previously.16


Profile of belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma.

Bodiford A, Bodge M, Talbott MS, Reddy NM - Onco Targets Ther (2014)

Pharmacology of histone deacetylase (HDAC) inhibitors.Note: Belinostat allows hyperacetylation of suppressed genes, resulting in cell growth and/or apoptosis in malignant cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4216035&req=5

f1-ott-7-1971: Pharmacology of histone deacetylase (HDAC) inhibitors.Note: Belinostat allows hyperacetylation of suppressed genes, resulting in cell growth and/or apoptosis in malignant cells.
Mentions: HDACi play a crucial role in the acetylation and deacetylation of histones and exert their action through removing acetyl groups from histones. The deacetylation of histones results in a more condensed chromatin structure, which causes transcriptional deactivation. Transcriptional deactivation allows undifferentiated growth and cell proliferation (Figure 1). Chromatin is found in the nucleus of many eukaryotic cells and is composed of DNA and proteins. A major function of chromatin is to protect DNA from damage. Histones are a major protein that comprise chromatin, and there has been increased interest over the past decade in the aberrant process of histone modifications, specifically histone acetylation. Levels of acetylation are balanced by histone acetyl-transferase and HDAC, and this balance plays a role in gene transcription/regulation as well as DNA repair. HDAC exerts its activity by removing acetyl groups from lysine located on histones, causing a more compact chromatin. This formation causes transcriptional gene silencing, resulting in increased potential for unregulated cell proliferation. There are approximately 18 different HDACs categorized into four classes, where HDACi inhibit class I and II. Class I HDACs regulate cell proliferation, while class II suppress apoptosis in malignant cells.14 Through this inhibition, HDACi exert its antineoplastic activity by allowing hyperacetylation of suppressed genes, resulting in cell growth arrest and/or apoptosis in malignant cells.15 A more comprehensive explanation of this mechanism of action has been described previously.16

Bottom Line: There is an urgent need to optimize induction therapy by incorporating novel agents that target the dysregulated pathways.Histone deacetylase inhibitors that induce acetylation of histones and enhance apoptosis have shown promising activity.In this article, we summarize the role of histone deacetylase inhibitors and specifically discuss pharmacokinetics, efficacy, and toxicity of the recently US Food and Drug Administration-approved agent belinostat for its use in patients with relapsed/refractory peripheral T-cell lymphoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA.

ABSTRACT
The peripheral T-cell lymphomas are a rare and heterogeneous group of mature T-cell lymphomas with limited available therapies. The outcome of frontline chemotherapy regimens has been disappointing, with a long-term survival of only 20%-30%. There is an urgent need to optimize induction therapy by incorporating novel agents that target the dysregulated pathways. Histone deacetylase inhibitors that induce acetylation of histones and enhance apoptosis have shown promising activity. In this article, we summarize the role of histone deacetylase inhibitors and specifically discuss pharmacokinetics, efficacy, and toxicity of the recently US Food and Drug Administration-approved agent belinostat for its use in patients with relapsed/refractory peripheral T-cell lymphoma.

No MeSH data available.


Related in: MedlinePlus