Epigenomics and interindividual differences in drug response.
Epigenomics is a rapidly growing field. New developments in epigenetics, such as the recently described modified cytosine variants (e.g., 5-hydroxymethylcytosine, 5hmC) and an arsenal of novel noncoding forms of RNA, can be applied in the area of drug pharmacokinetics and pharmacodynamics. Epigenetic aberrations can affect drug treatment by modulating the expressions of key genes involved in the metabolism and distribution of drugs as well as drug targets, thereby contributing to interindividual variation in drug response. These epigenetic alterations, along with the epigenetic profiles of circulating nucleic acids, have great potential to be used as biomarkers for personalized therapy, particularly in the treatment of cancer. In this review we present an update of pharmacoepigenetics with respect to epigenetic regulation of ADME genes (genes related to drug absorption, distribution, metabolism, and excretion) and drug targets, and we illustrate how this information can be used for predicting interindividual variations in drug response.