Epigenetic therapy combinations in acute myeloid leukemia: what are the options?
| العنوان: | Epigenetic therapy combinations in acute myeloid leukemia: what are the options? |
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| المؤلفون: | Maximilian Stahl, Jan Philipp Bewersdorf, Rory M. Shallis, Amer M. Zeidan |
| المصدر: | Therapeutic Advances in Hematology Therapeutic Advances in Hematology, Vol 10 (2019) |
| بيانات النشر: | SAGE Publications, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, acute myelogenous leukemia, epigenetic therapy, Decitabine, Review, acute myeloid leukemia, histone deacetylase inhibitors, Enasidenib, combination therapy, 03 medical and health sciences, 0302 clinical medicine, AML, histones, Histone methylation, Medicine, Epigenetics, DNA methylation, hypomethylating agent, lcsh:RC633-647.5, business.industry, lcsh:Diseases of the blood and blood-forming organs, Hematology, DOT1L, 030104 developmental biology, Hypomethylating agent, 030220 oncology & carcinogenesis, Cancer research, business, Epigenetic therapy, medicine.drug |
| الوصف: | Epigenetics refers to the regulation of gene expression mainly by changes in DNA methylation and modifications of histone proteins without altering the actual DNA sequence. While epigenetic modifications are essential for normal cell differentiation, several driver mutations in leukemic pathogenesis have been identified in genes that affect epigenetic processes, such as DNA methylation and histone acetylation. Several therapeutic options to target epigenetic alterations in acute myeloid leukemia (AML) have been successfully tested in preclinical studies and various drugs have already been approved for use in clinical practice. Among these already approved therapeutics are hypomethylating agents (azacitidine and decitabine) and isocitrate dehydrogenase inhibitors (ivosidenib, enasidenib). Other agents such as bromodomain-containing epigenetic reader proteins and histone methylation (e.g. DOT1L) inhibitors are currently in advanced clinical testing. As several epigenetic therapies have only limited efficacy when used as single agents, combination therapies that target AML pathogenesis at different levels and exploit synergistic mechanisms are also in clinical trials. Combinations of either epigenetic therapies with conventional chemotherapy, different forms of epigenetic therapies, or epigenetic therapies with immunotherapy are showing promising early results. In this review we summarize the underlying pathophysiology and rationale for epigenetically-based combination therapies, review current preclinical and clinical data and discuss the future directions of epigenetic therapy combinations in AML. |
| تدمد: | 2040-6215 2040-6207 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c59387f4ee33278c0ebcb12bf35d5966Test https://doi.org/10.1177/2040620718816698Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c59387f4ee33278c0ebcb12bf35d5966 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20406215 20406207 |
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