Abstract
Azanucleosides constitute the core therapy in the management of myelodysplastic syndromes (MDS), and have altered the treatment paradigm of MDS, previously dominated by supportive care strategies. DNA methylation regulates gene transcription in MDS, and it is hypothesized that azanucleoside therapy induces DNA hypomethylation and re-expression of aberrantly silenced genes in patients with these disorders. A series of clinical trials conducted over the past 5 years has demonstrated the activity of these therapies. Two agents, 5-azacitidine and decitabine, have been approved by the FDA for treatment of MDS. Recently, 5-azacitidine therapy has been shown, for the first time, to prolong survival in patients with MDS. Because the targeting of biologic pathways in MDS is best accomplished by combining agents with complementary mechanisms of action, combinations of azanucleosides with other drugs are being investigated. In this article, we critically appraise the most relevant clinical data reported on the use of azanucleosides for the treatment of patients with MDS.
Key Points
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Azanucleosides have significantly changed the outcome for patients with myelodysplastic syndrome (MDS), leading to an improvement in cytopenias and a reduction in the risk of transformation to acute myeloid leukemia
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It is hypothesized that azanucleosides act through induction of DNA hypomethylation, leading to re-expression of tumor suppressor genes that are silenced in cancer cells. However, there is still a lack of clinical data confirming this hypothesis
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One randomized trial demonstrated that 5-azacitidine improves survival in patients with MDS compared with conventional care regimens
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Decitabine leads to rapid responses and improvements in cytopenias in approximately 50% of patients with MDS, but no improvement in survival has been reported in clinical trials to date. A 5-day schedule of therapy may lead to better response rates than the original 3-day schedule
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Clinical studies combining azanucleosides with histone deacetylase inhibitors and other compounds (such as monoclonal antibodies) have been initiated
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Acknowledgements
A. Quintás-Cardama and F. P. S. Santos contributed equally to this manuscript. D. Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.
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Quintás-Cardama, A., Santos, F. & Garcia-Manero, G. Therapy with azanucleosides for myelodysplastic syndromes. Nat Rev Clin Oncol 7, 433–444 (2010). https://doi.org/10.1038/nrclinonc.2010.87
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DOI: https://doi.org/10.1038/nrclinonc.2010.87
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