Epigenomes as therapeutic targets.

Epigenetics is a molecular phenomenon that pertains to heritable changes in gene expression that do not involve changes in the DNA sequence. Epigenetic modifications in a whole genome, known as the epigenome, play an essential role in the regulation of gene expression in both normal development and disease. Traditional epigenetic changes include DNA methylation and histone modifications. Recent evidence reveals that other players, such as non-coding RNAs, may have an epigenetic regulatory role. Aberrant epigenetic signaling is becoming to be known as a central component of human disease, and the reversible nature of the epigenetic modifications provides an exciting opportunity for the development of clinically relevant therapeutics. Current epigenetic therapies provide a clinical benefit through disrupting DNA methyltransferases or histone deacetylases. However, the emergence of next-generation epigenetic therapies provides an opportunity to more effectively disrupt epigenetic disease states. Novel epigenetic therapies may improve drug targeting and drug delivery, optimize dosing schedules, and improve the efficacy of preexisting treatment modalities (chemotherapy, radiation, and immunotherapy). This review discusses the epigenetic mechanisms that contribute to the disease, available epigenetic therapies, epigenetic therapies currently in development, and the potential future use of epigenetic therapeutics in a clinical setting.