The role of epigenomics in personalized medicine

ABSTRACT

Introduction: Epigenetics is the study of reversible modifications to chromatin and their extensive and profound effects on gene regulation. To date, the role of epigenetics in personalized medicine has been under-explored. Therefore, this review aims to highlight the vast potential that epigenetics holds.

Areas covered: We first review the cell-specific nature of epigenetic states and how these can vary with developmental stage and in response to environmental factors. We then summarize epigenetic biomarkers of disease, with a focus on diagnostic tests, followed by a detailed description of current and pipeline drugs with epigenetic modes of action. Finally, we discuss epigenetic biomarkers of drug response.

Expert commentary: Epigenetic variation can yield information on cellular states and developmental histories in ways that genotype information cannot. Furthermore, in contrast to fixed genome sequence, epigenetic patterns are plastic, so correcting aberrant, disease-causing epigenetic marks holds considerable therapeutic promise. While just six epigenetic drugs are currently approved for use in the United States, a larger number is being developed. However, a drawback to current therapeutics is their non-specific effects. Development of locus-specific epigenetic modifiers, used in conjunction with epigenetic biomarkers of response, will enable truly precision interventions.

KEYWORDS:

• Chromatin remodeling
• DNA methylation
• DNMT inhibitors
• epigenetic biomarkers
• epigenetic drugs
• HDAC inhibitors
• histone modifications
• oncology
• neuroscience
• pharmacokinetics

Declaration of interest

JL McClay received honoraria from the American College of Clinical Pharmacy to present on the topic of pharmacoepigenomics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

JL McClay was partially supported by grant R21MH099419 from the US National Institutes of Health. MG Dozmorov was supported in part by the Virginia Commonwealth University Presidential Research Quest award. R Huang was supported by an American Cancer Society Institutional Research Grant. Sponsors had no role in the preparation of this manuscript.