Epigenetic drugs for cancer therapy

In mammalian cells, DNA can be modified by methylation of cytosine residues in CpG dinucleotides, and the N-terminal tails of histone proteins are subject to a wide range of different modifications, including acetylation, methylation, phosphorylation, and ubiquitylation. All of these chemical changes have a substantial influence on chromatin structure and gene expression. These epigenetic modification patterns can be regarded as heritable marks over many cell generations. Importantly, patterns and levels of DNA methylation and histone acetylation/deacetylation are profoundly altered in human cancers, which can result in altered gene expression of key regulator genes mainly involved in control of cell growth and proliferation, as well as DNA repair or maintenance of genome stability. Inhibitors of DNA methyltransferases and histone acetyltransferases/deacetylases have been shown to inhibit tumor growth by reactivating epigenetically silenced tumor suppressor genes and silencing oncogenes. Therefore, the use of epigenetic modulators such as anticancer compounds is a promising therapeutic strategy for cancer and other diseases.