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Curr Opin Oncol. 2005 Jan;17(1):55-60.

DNA methylation and cancer therapy: new developments and expectations.

Author information

1
Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO) Madrid, Spain. mesteller@cnio.es

Abstract

PURPOSE OF REVIEW:

In addition to having genetic causes, cancer can also be considered an epigenetic disease. The main epigenetic modification is DNA methylation, and patterns of aberrant DNA methylation are now recognized to be a common hallmark of human tumors. One of the most characteristic features is the inactivation of tumor-suppressor genes by CpG-island hypermethylation of the CpG islands located in their promoter regions. These sites, among others, are the targets of DNA-demethylating agents, the promising chemotherapeutic drugs that are the focus of this article.

RECENT FINDINGS:

Four exciting aspects have recently arisen at the forefront of the advancements in this field: first, the development of new compounds with DNA-demethylating capacity that are less toxic (for example, procaine) and may be administered orally (for example, zebularine); second, a better knowledge of the molecular mechanisms underlying the action of these drugs for particular genes and throughout the genome; third, the establishment of more reliable techniques to measure the effects of these drugs in clinical samples, such as high-performance capillary electrophoresis; and fourth, a decisive effort in the clinical trials that has merited the approval of 5-azacytidine by the U.S. Food and Drug Administration for the treatment of myelodysplastic syndrome.

SUMMARY:

We are at the dawn of an era when epigenetic drugs will be an important weapon in our arsenal in the war against cancer. Hematological malignancies have provided a promising starting point, but studies will surely extend to all solid tumors. However, we need to continue our research to develop more specific DNA-demethylating agents, to understand their biologic effects, and to determine whether they may be successfully combined with other epigenetic drugs, such as the inhibitors of histone deacetylases, and classic chemotherapy compounds.

PMID:
15608514
[Indexed for MEDLINE]

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