Epigenetic Modifications as Therapeutic Targets

Epigenetic modifications work with genetic mechanisms to determine transcriptional activity and, while somatically heritable they are also reversible, making them good therapeutic candidates. Epigenetic changes can precede disease pathology and thus are diagnostic indicators for risk, and can act as prognostic indicators for disease progression. Histone deacetylase inhibitors and DNA methylation inhibitors have been FDA approved for several years and are clinically successful. More recently, histone methylation and microRNAs have also gained attention as potential therapeutic targets. The presence of multiple epigenetic aberrations within a diseased tissue and the abilities of cells to develop resistance suggest that combination therapies may be most beneficial. This review will focus on recent examples of using epigenetic modifications to evaluate disease risk, progression and clinical response and will describe the latest clinical advances in epigenetic therapies concentrating on treatments which combine epigenetic therapeutics with each other and with cytotoxic agents to increase clinical response.