Pharmacoepigenomics

  • Image showing DNMT1, rather than DNMT3B, co-localizing with DNA double strand breaks (detected using gamma H2AX as a marker) in cells treated with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC).

Pharmacoepigenomics, the study of how epigenetics influences drug response, is an emerging area within the epigenetics field that has significant potential to impact patient care. A number of examples of interindividual variability in drug response leading to phenotypic consequences have been identified that cannot be associated with variations in gene sequence (the related science of pharmacogenomics). These are prime candidates for epigenetic variation influencing patient responses to drugs (for example, differences in DNA methylation patterns between individuals).

Several pharmacoepigenomic studies are in progress in the laboratory. In the first area, the mechanism of action of drugs that target DNA methylation, such as 5-azacytidine, is being studied to define how specific epigenetic landscapes and the mutational status of the epigenetic modifiers themselves modulate drug effects. In the second area, whole-genome short hairpin RNA screens are employed to identify genes and pathways that modulate efficacy of epigenetic-based inhibitors.

Each patient can potentially respond differently to their medication due to differences in the genome and epigenome that occur naturally or through a disease process. These differences may cause a medication to be less effective or result in greater than expected toxicity. Pharmacoepigenomics provides new markers to identify these interpatient responses and allow medications to be used in the most effective way.