Toward a Discipline of Pharmacoepigenomics

Moshe      Szyf

doi:10.2174/1570160043377358

Abstract

This review argues that the epigenome, which plays a critical role in controlling gene expression, plays also an important role in drug responsiveness. The epigenome is composed of chromatin and its modifications and DNA methylation. DNA methylation and chromatin structure are dynamic and tightly linked. Alterations in DNA methylation are involved in the pathology of cancer and in normal aging. It is suggested here that pharmacoepigenomics should be recognized as a new field in pharmacology. This field will address the epigenomic basis of issues which were traditionally the focus of pharmacogenetics and pharmacogenomics such as inter-individual differences in drug responsiveness, the impact of drugs on gene expression profiles, identification of unpredicted side effects of drugs at early stages of preclinical development and the discovery of novel drug targets. The reversibility of epigenetic states presents therapeutic and prophylactic opportunities, which necessitate the development of drugs that t arget the epigenomic machinery. Such drugs might be of therapeutic value in cancer and other diseases and in promoting and altering drug responsiveness.

Keywords: dna methylation, dna methyltransferase, chromatin structure, histone acetylation, histone methylation, histone deacetylases, methylated dna binding proteins, gene silencing, epigenomic states, drug-responsiveness