Pharmacoepigenetics: an element of personalized therapy?

ABSTRACT

Introduction: Epigenetics is a rapidly growing field describing heritable alterations in gene expression that do not involve DNA sequence variations. Advances in epigenetics and epigenomics have influenced pharmacology, leading to the development of a new specialty, pharmacoepigenetics, the study of the epigenetic basis for the individual variation in drug response.

Areas covered: We present an overview of the major epigenetic mechanisms and their effects on the expression of drug metabolizing enzymes and drug transporters, as well as the epigenetic status of drug protein targets affecting therapy response. Recent advances in the development of pharmacoepigenetic biomarkers and epidrugs are also discussed.

Expert opinion: There is growing evidence that pharmacoepigenetics has the potential to become an important element of personalized medicine. Epigenetic modifications influence drug response, but they can also be modulated by drugs. Moreover, they can be monitored not only in the affected tissue, but also in body fluids. Nevertheless, there are very few examples of epigenetic biomarkers implemented in the clinical setting. Explanation of the interplay between genomic and epigenomic changes will contribute to the personalized medicine approach. Ultimately, both genetic biomarkers and epigenetic mechanisms should be taken into consideration in predicting drug response in the course of successful personalized therapy.

KEYWORDS:

• Pharmacoepigenetics
• personalized medicine
• epigenetics
• DNA methylation
• histone modifications
• microRNA
• interindividual drug response

Article highlights

• Epigenetic alterations regulating the expression of drug metabolizing enzymes, nuclear receptors and transporters are associated with individual drug response, and provide explanation why patients with identical gene variants respond differently to therapy with a specific agent.

• Epigenetic changes in drug transporters are associated with acquired multidrug resistance and their modulation provides novel therapeutic options for cancer treatment.

• The number of epigenetic biomarkers for therapeutic response is increasing, with hypermethylation of MGMT being the most advanced example tested in the clinical setting.

• Epidrugs intervene in the epigenetic control of gene expression; some of them are already approved by U.S. FDA and numerous provide therapeutic benefit in clinical trials.

• Next generation sequencing and array technologies should improve unbiased biomarker identification and explain the interplay between genomic and epigenomic changes in cancer and other diseases. New methods for targeted pharmacogene analysis provide a good alternative to whole genome sequencing, and can contribute to personalized medicine approach.

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Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.