DMMC Course: UNRAVELLING CHROMATIN & THE ROLE OF EPIGENETICS IN DISEASE

1050-1110 Wednesday 26 April 2006. UCD Conway Institute Lecture Theatre

Epigenetics as a pharmacological target
Dr Helen Gallagher (UCD Conway Institute of Biomolecular & Biomedical Research)

Unlike mutations in DNA sequence, epigenetic changes, such as promoter hypermethylation and epigenetic silencing of tumor suppressor genes, are considered reversible, in that they must be maintained for their effects on gene function to persist within an organism. As a consequence of this reversibility, epigenetic changes are promising drug targets for the treatments of various diseases, most notably cancer. Several agents, which reverse promoter methylation or inhibit histone deacetylases, are under development for use in a variety of neoplastic diseases and results from preliminary clinical trials are promising. In this lecture, we will discuss the mechanisms of action of DNA methyltransferase inhibitors and histone deacetylase inhibitors. We also discuss future areas of pharmacological research in epigenetics, including the development of nonnucleoside inhibitors, and the need to define molecular endpoints so that changes induced in patients by demethylating drugs can be monitored during their treatment.