Pharmacogenetics and Personalized Drug Therapy

Journalist | Su Yeon Kim | sooyeon0112@yonsei.ac.kr

Designer

| Jin Yeong Kim | kimjin02000@yonsei.ac.kr

Pharmacogenetics is a field of study that investigates how genetic factors influence an individual’s response to drugs. According to a report by the American Medical Association, 2 million patients, which is 6.7% of all US patients, have been hospitalized due to serious adverse drug reactions even though they follow prescribed medication properly. Furthermore, among them, about a hundred thousand patients have experienced fatal drug reactions leading to death. This report indicates that some patients can experience adverse drug reactions even when taking medication as directed, not just due to drug misuse. Experts believe that it is due to genetic variations related to drug reactions. Therefore, if an individual’s genetic variation caused by drug reactions can be predicted in advance, personalized treatment would be efficient to prevent adverse reactions.

Personalized Drug Therapy Using Pharmacogenetics

1) Codeine, a narcotic pain reliever, is commonly used to suppress pain or coughing. It is effective only for individuals who possess specific genetic factors within their bodies. However, many people have taken the medicine without confirming its effectiveness. In the UK, it has been reported that about 8% of the population who take codeine do not experience its intended effects.

2) There are several endogenous drug receptors involved in the metabolism of anticancer drugs in the body. Depending on the genetic variations of these biomarker genes, the actual serum drug concentrations can vary greatly in patients. While medicines with a wide safety margin, such as antibiotics or other drugs, may show little difference in adverse reactions, anticancer drugs with a narrow safety margin can cause toxicity severely enough to be lifethreatening. For example, 5-Fluorouracil (5-FU), a representative anticancer drug, is metabolized in the body by dihydropyrimidine dehydrogenase (DPD). Patients with a congenital lack of DPD enzyme activity experience serious 5-FU toxicity, which could even lead to death.

3) The breast cancer treatment drug, Herceptin (Trastuzumab), is an immune-targeted therapy that selectively acts only on HER2 (human epidermal growth factor receptor 2). It is known to be effective only for breast cancer cells that produce an excess of HER2 protein without affecting normal cells. Therefore, it is used only when HER2 is positive according to genetic testing.

4) 6-Mercaptopurine (6-MP) and Azathioprine (AZA) are commonly used as drugs for the treatment of rare inflammatory bowel diseases. These drugs keep converting into inactive and active metabolites in the body, and during this process, important enzymes such as thiopurine S-methyltransferase (TPMT) play a role. The activity of this enzyme is determined by the genotype of the TPMT gene. Thus, by analyzing the TPMT genotype, the drug dosage can be determined to consider differences in efficacy and side effects between individuals, making it clinically useful.

Following the advancement of science, more and more genetic variations in individuals will be revealed in the future. If we discover biomarkers related to the drug response of each patient and develop genetic diagnostic tools, it will be possible to design a drug therapy for each individual. However, there are several challenges in applying personalized drug therapy based on pharmacogenomics in clinical practice. Even in the United States, data for interpreting genomic and genetic information used in actual clinical settings are insufficient. Also, clinicians have a lack of understanding of pharmacogenomics, which makes it difficult to apply it in clinical practice. To address these issues, the United States has established organizations such as CPIC and PharmGKB to provide data for clinical application, jointly research, and develop treatment guidelines based on the reaction between drugs and genomics. They also utilize health information technology (HIT) such as EMR and Clinical Decision Support systems (CDS) to support clinical decision-making and facilitate the implementation of personalized drug therapy in clinical settings. Likewise, in Korea, an effort for an advanced precision medical and pharmaceutical system is essential. In particular, people should prepare measures of personalized drug therapy based on pharmacogenomics through the introduction of a “specialized pharmacist system”. For example, in the field of organ transplantation medication, pharmacists are encouraged to learn how to adopt personalized drug therapy so that they can select adequate medication and decide the dosage of immunosuppressive agents based on each patient’s genotype. In this way, every patient will be able to get fully effective medication therapy by taking a genetic test only once in their lifetime. B