Epigenetic Therapy: a New Approach to Cancer Treatment

Dr. Peter Jones, professor of biochemistry and molecular biology at the University of Southern California (Los Angeles, USA) was the senior author of the study, published in the May 28, 2004, issue of Nature.

Epigenetic modifications to genes occur when chemical modifications to the DNA or the histones alter the structure of the chromatin without changing the nucleotide sequence of the DNA. Such changes to the structure of the chromatin have a profound influence on gene expression: if the chromatin is condensed, factors involved in gene expression cannot get to the DNA, and the genes will be switched off. Conversely, if the chromatin is "open,” the genes can be switched on if required.

While many heritable disorders are caused by mutations in the DNA that abolish gene expression, a number of human diseases are caused by inappropriate gene silencing, brought about by epigenetic modifications. Most cancers involve the epigenetic silencing of genes that normally control cell proliferation.

The major forms of epigenetic modification occurring in human tumors are DNA methylation and histone deacetylation. Several inhibitors of enzymes controlling these epigenetic modifications have shown promising antitumorigenic effects for some malignancies. These drugs include azacitidine and azadeoxycytidine, a more specific version of azacitidine that only affects DNA and thus potentially carries fewer side effects.




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