期刊
EXPERT OPINION ON INVESTIGATIONAL DRUGS
卷 20, 期 4, 页码 465-493出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/13543784.2011.559164
关键词
DNA methylation; epigenetics; histone modification; miRNA; myelodysplastic syndrome; therapy
资金
- Fondazione 'Amelia Scorza' Onlus, Cosenza, Italy
Areas covered: This review provides an understanding of studies investigating novel agents published up to January 2011 aimed at normalizing and monitoring the epigenetic profile of the MDS cancer cell. The authors discuss how non-intensive epigenetic therapy can ''re-programme'' gene expression patterns of abnormal hematopoiesis in MDS. Recently FDA-approved DNA-methyltransferase inhibitors, 5-azacytidine and 5-aza-2''-deoxycytidine or decitabine, represent frontline nonablative treatments, while combinations with histone deacetylase inhibitors show promising synergism in preclinical and Phase I/II trials in tumor suppressor gene re-expression and overall survival. Additional epigenetic mechanisms including non-encoding transcripts with inhibitory posttranscriptional regulatory functions, such as microRNAs, though not fully understood, present novel molecular and clinical implications in these disorders. Expert opinion: Alongside current single-agent epigenetic regimens, combination therapies represent potentially effective options for intermediate-2 and high-risk MDS. Methylation profiles and gene mutation predictors provide promising areas of development for monitoring MDS disease progression and outcome, while targeting microRNA dysregulation represents an important therapeutic goal.
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