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Clin Cancer Res. 2007 Mar 15;13(6):1634-7.

DNA methylation as a therapeutic target in cancer.

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  • 1University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. jpissa@mdanderson.org

Abstract

Targeting DNA methylation for cancer therapy has had a rocky history. The first reports on DNA methylation changes in cancer described global loss of methylation, which has been suggested to drive tumorigenesis through activation of oncogenic proteins or induction of chromosomal instability. In this context, reducing DNA methylation was viewed as a tumor-promoting event rather than a promising cancer therapy. The idea of inhibiting DNA methylation therapeutically emerged from subsequent studies showing that, in parallel to global decreases in methylation, several genes (including many critical to the tumor phenotype) displayed gains of methylation in their promoters during tumorigenesis, a process associated with epigenetic silencing of expression and loss of protein function. This led to revival of interest in drugs discovered decades ago to be potent inhibitors of DNA methyltransferases. These drugs have now been approved for clinical use in the United States in the treatment of myelodysplastic syndrome, thus opening the floodgate for a whole new approach to cancer therapy--epigenetic therapy.

PMID:
17363514
[PubMed - indexed for MEDLINE]
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