Journal
ANNALS OF INTERNAL MEDICINE
Volume 134, Issue 7, Pages 573-586Publisher
AMER COLL PHYSICIANS
DOI: 10.7326/0003-4819-134-7-200104030-00011
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Methylation of DNA is a biochemical modification that can influence gene expression acid is involved in inactivating one of the two X chromosomes in women, Evidence that has accumulated in the past 10 years suggests that cancer cells usurp this physiologic mechanism and use it to their benefit by inactivating tumor suppressor genes and related proteins. However, the primary structure of the affected proteins remains intact; reversal of abnormalities in DNA methylation may therefore restore the tumor-suppressive function of these genes and provide a novel approach to cancer therapy. Two demethylating drugs, 5-azacytidine and 5-azadeoxycytidine, are currently being tested in clinical trials, and several others are in preclinical development. In this article, the biological rationale for targeting aberrant methylation in cancer therapy is reviewed and completed phase I and II trials of this approach, some of which show promise for treatment of hematologic malignancies, are summarized.
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