Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents

Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,*1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, Australia*These authors contributed equally to this workAbstract: Hi...

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Autores principales:	Ververis K, Hiong A, Karagiannis TC, Licciardi PV
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/59ef244e4cd64ca2bf96ff421a175c18
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spelling	oai:doaj.org-article:59ef244e4cd64ca2bf96ff421a175c182021-12-02T04:03:52ZHistone deacetylase inhibitors (HDACIs): multitargeted anticancer agents1177-54751177-5491https://doaj.org/article/59ef244e4cd64ca2bf96ff421a175c182013-02-01T00:00:00Zhttp://www.dovepress.com/histone-deacetylase-inhibitors-hdacis-multitargeted-anticancer-agents-a12289https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, AustraliaThese authors contributed equally to this workAbstract: Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date.Keywords: chromatin modifications, histone acetylation, histone deacetylase inhibitor, suberoylanilide hydroxamic acid, depsipeptide, entinostatVerveris KHiong AKaragiannis TCLicciardi PVDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2013, Iss default, Pp 47-60 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Ververis K Hiong A Karagiannis TC Licciardi PV Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents
description	Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, AustraliaThese authors contributed equally to this workAbstract: Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date.Keywords: chromatin modifications, histone acetylation, histone deacetylase inhibitor, suberoylanilide hydroxamic acid, depsipeptide, entinostat
format	article
author	Ververis K Hiong A Karagiannis TC Licciardi PV
author_facet	Ververis K Hiong A Karagiannis TC Licciardi PV
author_sort	Ververis K
title	Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents
title_short	Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents
title_full	Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents
title_fullStr	Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents
title_full_unstemmed	Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents
title_sort	histone deacetylase inhibitors (hdacis): multitargeted anticancer agents
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/59ef244e4cd64ca2bf96ff421a175c18
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Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents

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