Clinical use and applications of histone deacetylase inhibitors in multiple myeloma

Nidhi Tandon, Vijay Ramakrishnan, Shaji K Kumar Division of Hematology, Mayo Clinic, Rochester, MN, USA Abstract: The incorporation of various novel therapies has resulted in a significant survival benefit in newly diagnosed and relapsed patients with multiple myeloma (MM) over the past decade. Des...

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Autores principales:	Tandon N, Ramakrishnan V, Kumar SK
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Histone deacetylase inhibitors myeloma relapse Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/26d3b8dbfff24a37b6b8c41b820ae08f
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spelling	oai:doaj.org-article:26d3b8dbfff24a37b6b8c41b820ae08f2021-12-02T06:34:46ZClinical use and applications of histone deacetylase inhibitors in multiple myeloma1179-1438https://doaj.org/article/26d3b8dbfff24a37b6b8c41b820ae08f2016-05-01T00:00:00Zhttps://www.dovepress.com/clinical-use-and-applications-of-histone-deacetylase-inhibitors-in-mul-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Nidhi Tandon, Vijay Ramakrishnan, Shaji K Kumar Division of Hematology, Mayo Clinic, Rochester, MN, USA Abstract: The incorporation of various novel therapies has resulted in a significant survival benefit in newly diagnosed and relapsed patients with multiple myeloma (MM) over the past decade. Despite these advances, resistance to therapy leads to eventual relapse and fatal outcomes in the vast majority of patients. Hence, there is an unmet need for new safe and efficacious therapies for continued improvement in outcomes. Given the role of epigenetic aberrations in the pathogenesis and progression of MM and the success of histone deacetylase inhibitors (HDACi) in other malignancies, many HDACi have been tried in MM. Various preclinical studies helped us to understand the antimyeloma activity of different HDACi in MM as a single agent or in combination with conventional, novel, and immune therapies. The early clinical trials of HDACi depicted only modest single-agent activity, but recent studies have revealed encouraging clinical response rates in combination with other antimyeloma agents, especially proteasome inhibitors. This led to the approval of the combination of panobinostat and bortezomib for the treatment of relapsed/refractory MM patients with two prior lines of treatment by the US Food and Drug Administration. However, it remains yet to be defined how we can incorporate HDACi in the current therapeutic paradigms for MM that will help to achieve longer disease control and significant survival benefits. In addition, isoform-selective and/or class-selective HDAC inhibition to reduce unfavorable side effects needs further evaluation. Keywords: HDAC inhibitors, Panobinostat, epigenetics, myeloma, relapseTandon NRamakrishnan VKumar SKDove Medical PressarticleHistone deacetylase inhibitorsmyelomarelapseTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2016, Iss Issue 1, Pp 35-44 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Histone deacetylase inhibitors myeloma relapse Therapeutics. Pharmacology RM1-950
spellingShingle	Histone deacetylase inhibitors myeloma relapse Therapeutics. Pharmacology RM1-950 Tandon N Ramakrishnan V Kumar SK Clinical use and applications of histone deacetylase inhibitors in multiple myeloma
description	Nidhi Tandon, Vijay Ramakrishnan, Shaji K Kumar Division of Hematology, Mayo Clinic, Rochester, MN, USA Abstract: The incorporation of various novel therapies has resulted in a significant survival benefit in newly diagnosed and relapsed patients with multiple myeloma (MM) over the past decade. Despite these advances, resistance to therapy leads to eventual relapse and fatal outcomes in the vast majority of patients. Hence, there is an unmet need for new safe and efficacious therapies for continued improvement in outcomes. Given the role of epigenetic aberrations in the pathogenesis and progression of MM and the success of histone deacetylase inhibitors (HDACi) in other malignancies, many HDACi have been tried in MM. Various preclinical studies helped us to understand the antimyeloma activity of different HDACi in MM as a single agent or in combination with conventional, novel, and immune therapies. The early clinical trials of HDACi depicted only modest single-agent activity, but recent studies have revealed encouraging clinical response rates in combination with other antimyeloma agents, especially proteasome inhibitors. This led to the approval of the combination of panobinostat and bortezomib for the treatment of relapsed/refractory MM patients with two prior lines of treatment by the US Food and Drug Administration. However, it remains yet to be defined how we can incorporate HDACi in the current therapeutic paradigms for MM that will help to achieve longer disease control and significant survival benefits. In addition, isoform-selective and/or class-selective HDAC inhibition to reduce unfavorable side effects needs further evaluation. Keywords: HDAC inhibitors, Panobinostat, epigenetics, myeloma, relapse
format	article
author	Tandon N Ramakrishnan V Kumar SK
author_facet	Tandon N Ramakrishnan V Kumar SK
author_sort	Tandon N
title	Clinical use and applications of histone deacetylase inhibitors in multiple myeloma
title_short	Clinical use and applications of histone deacetylase inhibitors in multiple myeloma
title_full	Clinical use and applications of histone deacetylase inhibitors in multiple myeloma
title_fullStr	Clinical use and applications of histone deacetylase inhibitors in multiple myeloma
title_full_unstemmed	Clinical use and applications of histone deacetylase inhibitors in multiple myeloma
title_sort	clinical use and applications of histone deacetylase inhibitors in multiple myeloma
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/26d3b8dbfff24a37b6b8c41b820ae08f
work_keys_str_mv	AT tandonn clinicaluseandapplicationsofhistonedeacetylaseinhibitorsinmultiplemyeloma AT ramakrishnanv clinicaluseandapplicationsofhistonedeacetylaseinhibitorsinmultiplemyeloma AT kumarsk clinicaluseandapplicationsofhistonedeacetylaseinhibitorsinmultiplemyeloma
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Clinical use and applications of histone deacetylase inhibitors in multiple myeloma

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