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From a Better Understanding of the Mechanisms of Action of Histone Deacetylases Inhibitors to the Progress of the Treatment of Malignant Lymphomas and Plasma Cell Myeloma
被引:1
|作者:
Mihaila, Romeo G.
[1
]
机构:
[1] Lucian Blaga Univ Sibiu, Fac Med, Emergency Cty Clin Hosp Sibiu, Sibiu, Romania
关键词:
Apoptosis;
cutaneous T-cell lymphoma;
epigenetics;
gene expression;
histone deacetylases;
histone deacetylases inhibitor;
multiple myeloma;
peripheral T-cell lymphoma;
CUTANEOUS T-CELL;
REFRACTORY MULTIPLE-MYELOMA;
SELECTIVE HDAC6 INHIBITOR;
OPEN-LABEL;
SYNERGISTIC CYTOTOXICITY;
HEMATOLOGIC MALIGNANCIES;
INDUCED APOPTOSIS;
INDUCE APOPTOSIS;
HODGKIN LYMPHOMA;
PHASE-II;
D O I:
10.2174/1574892812666170920110054
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Background: Notable progress has been made in chemo- and immunotherapy of B-cell lymphomas, but less in the treatment of T-cell lymphomas. Objective: Histone deacetylases inhibitors are a potentially useful therapeutic mean, as an epigenetic dysregulation is present in lymphomas, and especially in T-cell types. We aimed to study the progress made in this area. Method: A mini-review was achieved using the articles published in PubMed in the last two years and the new patents made in this field. Results: Histone deacetylases inhibitors are involved in the derepression of tumor suppressor genes through a histone deacetylase-mediated transcriptional process. Their inhibition is followed by cell cycle arrest, cell differentiation, apoptosis, sometimes autophagy, and a reversal of the transformed phenotype. They can also remove the resistance to chemo-or immunotherapy through different pathways. Some of them, as romidepsin, may decrease the protein level of multi-drug resistance associated protein 1, followed by a decrease in cellular drug export activity for DNA alkylating agents. Some compounds are approved for relapsed/refractory T-cell lymphomas or multiple myeloma treatment. The recent patents and the clinical trials with a histone deacetylases inhibitor administred in a synergistic drug combination with a demethylating, immunomodulatory, or anticancer agent as well as the discovery of more selective histone deacetylases inhibitors, with fewer side effects, could be a way to increase the treatment efficacy. Conclusion: New and more effective histone deacetylases inhibitors given alone or in drug combination are a solution for an improved response to the treatment of patients with relapsed/refractory lymphoproliferative disorders.
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页码:283 / 295
页数:13
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