期刊
EXPERT OPINION ON INVESTIGATIONAL DRUGS
卷 25, 期 3, 页码 307-317出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/13543784.2016.1146251
关键词
Immunotherapy; MDS; Epigenetics; AML; HDACi based combination therapy; myeloid malignancies; HDACi; Hypomethylating agents; Histone deacetylase inhibitors; Vorinostat
资金
- Merck Sharp and Doehme
- Syndax
- Celgene
Introduction: Epigenetic changes and mutations in epigenetic modifiers characterize and likely drive many cases of acute myeloid leukemia and myelodysplastic syndrome. Development of DNA methyltransferase inhibitors has been most successful in these diseases. While many epigenetic marks are potential targets of cancer therapies, histone deacetylase inhibitors (HDACi) have undergone the most advanced development to date. Area Covered: In this review, the authors describe and discuss the biology and the clinical results of HDAC inhibitors in the settings of myeloid malignancies. Expert opinion: While significant results have been achieved in lymphoma and myeloma, efficacy remains limited in myeloid malignancies for both single agent and HDACi based combination regimens. The redundancy and the pleiotropic activity of HDACi (on both histone and non-histone proteins) are key factors that have limited to date the selection of patients and the design of robust biomarkers. Recent advances in biology (mechanisms of resistance, immunology) and the design of a more specific third generation of HDACi are two important features that will drive the future clinical development of HDACi in myeloid malignancies.
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