Cargando…
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...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730337/ https://www.ncbi.nlm.nih.gov/pubmed/24216985 http://dx.doi.org/10.3390/cancers5020430 |
_version_ | 1782279062238003200 |
---|---|
author | Maes, Ken Menu, Eline Van Valckenborgh, Els Van Riet, Ivan Vanderkerken, Karin De Bruyne, Elke |
author_facet | Maes, Ken Menu, Eline Van Valckenborgh, Els Van Riet, Ivan Vanderkerken, Karin De Bruyne, Elke |
author_sort | Maes, Ken |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3730337 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-37303372013-08-05 Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma Maes, Ken Menu, Eline Van Valckenborgh, Els Van Riet, Ivan Vanderkerken, Karin De Bruyne, Elke Cancers (Basel) Review 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. MDPI 2013-04-15 /pmc/articles/PMC3730337/ /pubmed/24216985 http://dx.doi.org/10.3390/cancers5020430 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Review Maes, Ken Menu, Eline Van Valckenborgh, Els Van Riet, Ivan Vanderkerken, Karin De Bruyne, Elke Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma |
title | 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_short | Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma |
title_sort | epigenetic modulating agents as a new therapeutic approach in multiple myeloma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730337/ https://www.ncbi.nlm.nih.gov/pubmed/24216985 http://dx.doi.org/10.3390/cancers5020430 |
work_keys_str_mv | AT maesken epigeneticmodulatingagentsasanewtherapeuticapproachinmultiplemyeloma AT menueline epigeneticmodulatingagentsasanewtherapeuticapproachinmultiplemyeloma AT vanvalckenborghels epigeneticmodulatingagentsasanewtherapeuticapproachinmultiplemyeloma AT vanrietivan epigeneticmodulatingagentsasanewtherapeuticapproachinmultiplemyeloma AT vanderkerkenkarin epigeneticmodulatingagentsasanewtherapeuticapproachinmultiplemyeloma AT debruyneelke epigeneticmodulatingagentsasanewtherapeuticapproachinmultiplemyeloma |