Recent patents on anti-cancer drug discovery · 2017
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.
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Mihaila Romeo G
Аннотация
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.
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.