Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a the...

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Published in	Frontiers in oncology Vol. 8; p. 92
Main Authors	Suraweera, Amila, O’Byrne, Kenneth J., Richard, Derek J.
Format	Journal Article
Language	English
Published	Switzerland Frontiers Media S.A 29.03.2018
Subjects	cancer chemotherapeutic drugs combination therapy histone deacetylase inhibitors histone deacetylases Oncology combination therapy histone deacetylases cancer chemotherapeutic drugs histone deacetylase inhibitors
Online Access	Get full text
ISSN	2234-943X 2234-943X
DOI	10.3389/fonc.2018.00092

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Abstract	Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, HDACi have shown limited success in treating solid tumors. The combination of HDACi with standard chemotherapeutic drugs has demonstrated promising anticancer effects in both preclinical and clinical studies. In this review, we summarize the research thus far on HDACi in combination therapy, with other anticancer agents and their translation into preclinical and clinical studies. We additionally highlight the side effects associated with HDACi in cancer therapy and discuss potential biomarkers to either select or predict a patient's response to these agents, in order to limit the off-target toxicity associated with HDACi.
AbstractList	Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, HDACi have shown limited success in treating solid tumors. The combination of HDACi with standard chemotherapeutic drugs has demonstrated promising anticancer effects in both preclinical and clinical studies. In this review, we summarize the research thus far on HDACi in combination therapy, with other anticancer agents and their translation into preclinical and clinical studies. We additionally highlight the side effects associated with HDACi in cancer therapy and discuss potential biomarkers to either select or predict a patient's response to these agents, in order to limit the off-target toxicity associated with HDACi.Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, HDACi have shown limited success in treating solid tumors. The combination of HDACi with standard chemotherapeutic drugs has demonstrated promising anticancer effects in both preclinical and clinical studies. In this review, we summarize the research thus far on HDACi in combination therapy, with other anticancer agents and their translation into preclinical and clinical studies. We additionally highlight the side effects associated with HDACi in cancer therapy and discuss potential biomarkers to either select or predict a patient's response to these agents, in order to limit the off-target toxicity associated with HDACi. Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, HDACi have shown limited success in treating solid tumors. The combination of HDACi with standard chemotherapeutic drugs has demonstrated promising anticancer effects in both preclinical and clinical studies. In this review, we summarize the research thus far on HDACi in combination therapy, with other anticancer agents and their translation into preclinical and clinical studies. We additionally highlight the side effects associated with HDACi in cancer therapy and discuss potential biomarkers to either select or predict a patient’s response to these agents, in order to limit the off-target toxicity associated with HDACi.
Author	O’Byrne, Kenneth J. Suraweera, Amila Richard, Derek J.
AuthorAffiliation	2 Princess Alexandra Hospital , Brisbane, QLD , Australia 1 School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology , Brisbane, QLD , Australia
AuthorAffiliation_xml	– name: 2 Princess Alexandra Hospital , Brisbane, QLD , Australia – name: 1 School of Biomedical Research, Institute of Health and Biomedical Innovation at the Translational Research Institute, Queensland University of Technology , Brisbane, QLD , Australia
Author_xml	– sequence: 1 givenname: Amila surname: Suraweera fullname: Suraweera, Amila – sequence: 2 givenname: Kenneth J. surname: O’Byrne fullname: O’Byrne, Kenneth J. – sequence: 3 givenname: Derek J. surname: Richard fullname: Richard, Derek J.
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/29651407$$D View this record in MEDLINE/PubMed
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Keywords	combination therapy histone deacetylases cancer chemotherapeutic drugs histone deacetylase inhibitors
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SubjectTerms	cancer chemotherapeutic drugs combination therapy histone deacetylase inhibitors histone deacetylases Oncology
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Title	Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi
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