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.

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.