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Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma

Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussel, Belgium
Stem Cell Laboratory, Department Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussel, Belgium
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2013, 5(2), 430-461;
Received: 28 February 2013 / Revised: 3 April 2013 / Accepted: 8 April 2013 / Published: 15 April 2013
(This article belongs to the Special Issue Cancer Epigenetics)
PDF [954 KB, uploaded 15 April 2013]


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. View Full-Text
Keywords: multiple myeloma; epigenetics; histone deacetylase inhibitor; DNA-methyltransferase inhibitor multiple myeloma; epigenetics; histone deacetylase inhibitor; DNA-methyltransferase inhibitor

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Maes, K.; Menu, E.; Van Valckenborgh, E.; Van Riet, I.; Vanderkerken, K.; De Bruyne, E. Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma. Cancers 2013, 5, 430-461.

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