Epigenetic transcriptional repression of tumor suppresor genes and its reversion by drugs.

2005

Genetic alterations and deregulation of the epigenetic mechanisms collaborate in the initiation and progression of cancer. In contrast to the genetic defects, the epigenetic abnormalities are potentially reversible. This fact has driven the search for drugs that induce selectively changes in the epigenetic patterns of the tumor cells and thus lead to differentiation, cell death and/or cell growth arrest. Inhibitors of DNA (cytosine-5)-methyltransferases (DNMTs) and inhibitors of Zn(II)-dependent histone deacetylases (HDACs) have been developed with this purpose. The DNMTs inhibitors allow the reactivation of genes, including tumor-suppressor genes, silenced through hypermethylation of the C…