Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma
Multiple myeloma (MM) is an incurable B-cell malignancy. Therefore, new targets and drugs are urgently needed to improve patient outcome. Epigenetic aberrations play a crucial role in development and progression in cancer, including MM. To target these aberrations, epigenetic modulating agents, such...
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doaj-4e325c52fb844a2a82e359fb2c405d392020-11-24T23:01:11ZengMDPI AGCancers2072-66942013-04-015243046110.3390/cancers5020430Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple MyelomaElke De BruyneKarin VanderkerkenIvan Van RietKen MaesEline MenuEls Van ValckenborghMultiple myeloma (MM) is an incurable B-cell malignancy. Therefore, new targets and drugs are urgently needed to improve patient outcome. Epigenetic aberrations play a crucial role in development and progression in cancer, including MM. To target these aberrations, epigenetic modulating agents, such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), are under intense investigation in solid and hematological cancers. A clinical benefit of the use of these agents as single agents and in combination regimens has been suggested based on numerous studies in pre-clinical tumor models, including MM models. The mechanisms of action are not yet fully understood but appear to involve a combination of true epigenetic changes and cytotoxic actions. In addition, the interactions with the BM niche are also affected by epigenetic modulating agents that will further determine the in vivo efficacy and thus patient outcome. A better understanding of the molecular events underlying the anti-tumor activity of the epigenetic drugs will lead to more rational drug combinations. This review focuses on the involvement of epigenetic changes in MM pathogenesis and how the use of DNMTi and HDACi affect the myeloma tumor itself and its interactions with the microenvironment.http://www.mdpi.com/2072-6694/5/2/430multiple myelomaepigeneticshistone deacetylase inhibitorDNA-methyltransferase inhibitor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elke De Bruyne Karin Vanderkerken Ivan Van Riet Ken Maes Eline Menu Els Van Valckenborgh |
spellingShingle |
Elke De Bruyne Karin Vanderkerken Ivan Van Riet Ken Maes Eline Menu Els Van Valckenborgh Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma Cancers multiple myeloma epigenetics histone deacetylase inhibitor DNA-methyltransferase inhibitor |
author_facet |
Elke De Bruyne Karin Vanderkerken Ivan Van Riet Ken Maes Eline Menu Els Van Valckenborgh |
author_sort |
Elke De Bruyne |
title |
Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma |
title_short |
Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma |
title_full |
Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma |
title_fullStr |
Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma |
title_full_unstemmed |
Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma |
title_sort |
epigenetic modulating agents as a new therapeutic approach in multiple myeloma |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2013-04-01 |
description |
Multiple myeloma (MM) is an incurable B-cell malignancy. Therefore, new targets and drugs are urgently needed to improve patient outcome. Epigenetic aberrations play a crucial role in development and progression in cancer, including MM. To target these aberrations, epigenetic modulating agents, such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi), are under intense investigation in solid and hematological cancers. A clinical benefit of the use of these agents as single agents and in combination regimens has been suggested based on numerous studies in pre-clinical tumor models, including MM models. The mechanisms of action are not yet fully understood but appear to involve a combination of true epigenetic changes and cytotoxic actions. In addition, the interactions with the BM niche are also affected by epigenetic modulating agents that will further determine the in vivo efficacy and thus patient outcome. A better understanding of the molecular events underlying the anti-tumor activity of the epigenetic drugs will lead to more rational drug combinations. This review focuses on the involvement of epigenetic changes in MM pathogenesis and how the use of DNMTi and HDACi affect the myeloma tumor itself and its interactions with the microenvironment. |
topic |
multiple myeloma epigenetics histone deacetylase inhibitor DNA-methyltransferase inhibitor |
url |
http://www.mdpi.com/2072-6694/5/2/430 |
work_keys_str_mv |
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