Acetylation and Histone Deacetylase Inhibitors in Cancer

Abstract

In recent years, the role of epigenetics in the development and treatment of cancer has gained interest and the effects of internal and external factors on the epigenetic profile are under investigation. The term “epigenetics” refers to modifications that influence phenotype without altering genotype. Epigenetic changes are potentially reversible but generally stably maintained during the cell cycle. Since Feinberg et al. described differences in DNA methylation in human cancer in 1983 [66], several mechanisms of epigenetic control have been identified such as DNA methylation and histone modifications including acetylation, methylation and phosphorylation. Recently Seligson et al. reported that specific histone modification patterns are predictive of the risk of prostate cancer recurrence [183] and Fraga et al. showed that a profound disruption in histone modification patterns is a common feature of cancer [70]. Epigenetic abnormalities can be acquired during fetal development and during the course of a life contributing to common cancer risk in adults [65]. Recently Fraga et al. reported that, although monozygotic twins are epigenetically identical during the first years of life, the patterns of global and locus specific epigenetic modifications and gene expression patterns in monozygotic twin pairs diverge as they become older [70]. These differences could be explained by the influence of external factors such as smoking, physical activity and diet [17,61] as well as by accumu-