Pharmacoepigenetics is an emerging field that studies the underlying epigenetic marking patterns that lead to variation in an individual's response to medical treatment.

Due to genetic heterogeneity, environmental factors, and pathophysiological causes, individuals that exhibit similar disease expression may respond differently to identical drug treatments. Selecting treatments based on factors such as age, body-surface area, weight, gender, or disease stage has been shown to incompletely address this problem, so medical professionals are shifting toward using patient genomic data to select optimal treatments. Now, an increasing amount of evidence shows that epigenetics also plays an important role in determining the safety and efficacy of drug treatment in patients. Epigenetics is a bridge that connects individual genetics and environmental factors to explain some aspects of gene expression. Specifically, environmental factors have the potential to alter one's epigenetic mechanisms in order to influence the expression of genes. For example, smoking cigarettes can alter the DNA methylation state of genes and thereby expression of genes through different mechanisms.

Epigenetic changes in genes caused by factors such as environment can result in abnormal gene expression and the initiation of diseases. The progression of diseases further alters the epigenetic patterns of the whole genome. While epigenetic changes are generally long lasting, and in some cases permanent, there is still the potential to change the epigenetic state of a gene. Thus, drugs have been developed to target aberrant epigenetic patterns in cells to either activate or suppress the epigenetically modified gene expression gene expression. This is known as epigenetic therapy. Besides being drug targets, epigenetic changes are also used as diagnostic and prognostic indicators to predict disease risk and progression, and this could be beneficial for the improvement of personalized medicine.

The development of the Human Epigenome Project and advances in epigenomics has given rise to a burgeoning field known as pharmacoepigenetics. Pharmacoepigenetics was initially developed to study how epigenetic patterns of drug transporters, drug-metabolizing enzymes, and nuclear receptors affect individuals’ response to the drug. Now, pharmacoepigenetics has an additional focus: the development of therapeutic epidrugs that can make changes to the epigenome in order to lessen the cause or symptoms of a disease in an individual. Even though a large gap still remains between the knowledge of epigenetic modifications on drug metabolism mechanisms and clinical applications, pharmacoepigenetics has become a rapidly growing field that has the potential to play an important role in personalized medicine.

In order to develop effective epigenetic therapies, it is important to understand the underlying epigenetic mechanisms and the proteins that are involved. Various mechanisms and modifications play a role in epigenetic remodeling and signaling, including DNA methylation, histone modification, covalent modifications, RNA transcripts, microRNAs, mRNA, siRNA, and nucleosome positioning. In particular, scientists have extensively studied the associations of DNA methylation, histone modifications, regulatory microRNA with the development of diseases.

DNA methylation is the most widely studied epigenetic mechanism. Most of them occur at CpG sites. DNA methyltransferase is recruited to the site and adds methyl groups to the cytosine of the CpG dinucleotides. This allows the methyl-CpG binding proteins to bind to the methylated site and cause downregulation of genes. Histone modification is mainly achieved by modifying the N-terminal tails of histones. The mechanisms include acetylation, methylation, phosphorylation, unbiquitination, etc. They affect the compaction of chromatin structure, the accessibility of the DNA, and therefore the transcriptional level of specific genes.

Additionally, microRNA is a type of noncoding RNA that is responsible for altering gene expression by targeting and marking mRNA transcripts for degradation. Since this process is a posttranscriptional modification, it does not involve changes in DNA sequence. The expression of microRNA is also regulated by other epigenetic mechanisms. Aberrant expression of microRNA facilitates disease development, making them good targets for epigenetic therapies. Epigenetic proteins involved in the regulation of gene transcription fall into three categories-writers, erasers, and readers. Both writers and erasers have enzymatic activity that allows them to covalently modify DNA or histone proteins. Readers have the ability to recognize and bind to specific sites on chromatin to alter epigenetic signatures.

Once the underlying epigenetic mechanisms are understood, it becomes possible to develop new ways to alter epigenetic marks such as "epidrugs", or epigenome editing, which is the overwriting of epigenetic patterns using man-made signals to direct epigenetic proteins to target loci. Furthermore, based on patients' unique epigenetic patterns, medical professionals can more accurately assign a safe and effective treatment including appropriate epigenetic drugs tailored to the patient.