Pharmacogenomics

Pharmacogenomics is the study of how a person's genes will affect his or her body's response to various drugs and medical treatments. This relatively new field of medicine combines pharmacology, the study of drugs, and genomics, the study of genes and their functions, to develop safe medications specific to a patient's genetic makeup. The study is sometimes referred to as drug-gene testing or pharmacogenetics. Testing through pharmacogenomics allows a health provider to determine the best medication for a patient, or find out why a patient may be having an adverse reaction to a drug or treatment. Through testing a small sample of blood or saliva, clinical professionals can determine an effective medication or treatment for a patient, what dosing amount is best for that patient, and whether the patient could have serious side effects from a medication.

Background

Before the development of pharmacogenomics, drugs were believed to be mostly "one size fits all." In other words, they were thought to work the same in nearly every patient. Genomic research challenged that notion and allowed for more personalized approaches to medicine and the treatment of diseases. The building blocks of the study of pharmacogenomics date back to the 1950s, when clinical observations were made regarding the impact genetics had on drug disposition and drug effects. Dr. Werner Kalow published a landmark paper in 1956 in which he described several patients who did not exhibit a typical response to a drug due to a genetic variation. Several similar studies by other scientists followed and, in 1959, a scientist named Friedrich Vogel used the term pharmacogenetics for the first time.

Pharmacogenomics became an established scientific discipline in the 1950s, and studies continued to expand throughout the following decade. It was not until the early 1970s that another major expansion in the field occurred when scientists noted several genetic variations in key drug metabolizing enzymes in the liver. A study published in 1977 noted measurable differences in elimination of an antihypertensive drug in ninety-four volunteers. It was determined that the volunteers had different reactions to the drug due to genetic variations in an enzyme later identified as cytochrome p450, 2D6, or CYP2D6. Since that initial finding, numerous other drugs have shown to be substrates, which are the substances on which an enzyme acts, for CYP2D6, and, therefore, could be affected by the genetic variation in that enzyme.

In the 1980s, genetic differences were identified in other drug metabolizing enzymes. In 1988, Congress commissioned the formation of the Human Genome Project, which aimed to sequence the entire human genome. The National Institutes of Health (NIH) and the Department of Energy ran the project. The final results of the project were presented in 2003. Through that research, the NIH established the Pharmacogenomics Research Network, or PGRN, in 2000. The PGRN is a collaboration of scientists with the goal of examining the relationship between genetic variation and drug response to provide a resource that allows researchers to interact, share knowledge, and create a public database for medical professionals and others to access information.

Overview

In the twenty-first century, health care providers are using information garnered from pharmacogenomics to prescribe drugs, though such tests are routine for only a small number of health problems. Given the field's quick growth, researchers hope it can one day become a tool to help better manage heart disease, cancer, asthma, depression, and other common diseases. One modern use of pharmacogenomics involves patients who have human immunodeficiency virus (HIV). Pharmacogenomics allows doctors to test HIV patients for a genetic variant that would make them more likely to have a reaction to the antiviral drug abacavir. Another example is found in how pharmacogenomics can help cancer patients fight their disease. For instance, studies have shown that certain chemotherapy drugs work better in lung cancer patients whose tumors have a certain genetic code; the same is true for the breast cancer drug trastuzumab. Leukemia patients with a certain genetic profile can have serious side effects from the chemotherapy drug mercaptopurine. Pharmacogenomics can help doctors recognize these patients and get them the drugs they need.

Areas of focus for ongoing pharmacogenomics research include other cancer treatments; blood thinners; and selective serotonin reuptake inhibitors (SSRIs), a class of drug that is widely used in the treatment of depression. In all of these cases, a patient being given a drug that does not work for them can have serious, even fatal, consequences; being able to reduce the uncertainty about the effectiveness of particular drugs for a specific patient is therefore a high priority.

In addition to helping health care providers determine which drug is right for a patient, scientists hope pharmacogenomics can lead to the development of new drugs that are more effective and cause fewer side effects. Researchers are using genomic information to create drugs aimed at subgroups of patients with specific genetic profiles. Data garnered through pharmacogenomics is also helping researchers to search for drugs that would target specific molecular and cellular pathways involved in disease.

Although the study of pharmacogenomics has proved beneficial in helping health care providers to better select drugs for their patients, the field does have limitations. For example, one single test cannot determine how a patient will respond to all medications. Since the tests are drug-specific, patients would need to take more than one test if they are taking more than one medication. The tests are also not available for all medications, including aspirin and many over-the-counter pain relievers. Pharmacogenomics also cannot reveal the perfect drug for a specific patient with a specific condition or provide information on drug-to-drug interactions.

Unlike other genetic tests, pharmacogenomics does not measure disease risk but rather it helps doctors identify treatments that are most likely to work for an already diagnosed condition. However, the tests do have value throughout a patient's life. Since genes do not change over time, patients would only need one test to discover genetic information that could then be applied to their future care. Through studying a set of a patient's genes, health care providers can analyze a broad amount of information regarding drug therapy for many conditions, information that can then be stored in a patient's medical record for future use.

Bibliography

Altman, Russ B., David Flockhart, and David B. Goldstein. Principles of Pharmacogenetics and Pharmacogenomics. Cambridge University Press, 2012.

Borden, Brittany A., and Peter H. O'Donnell. "Implementing Preemptive Pharmacogenomics in Clinical Practice." Clinical Laboratory News, 1 Apr. 2018, www.aacc.org/publications/cln/articles/2018/april/implementing-preemptive-pharmacogenomics-in-clinical-practice. Accessed 28 Sept. 2018.

"Drug-Gene Testing." Mayo Clinic, mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-testing.asp. Accessed 8 Apr. 2017

Dunnenberger, Mark. "7 Things to Know about Pharmacogenomics." U.S. News & World Report, 1 Aug. 2016, health.usnews.com/health-news/patient-advice/articles/2016-08-01/7-things-to-know-about-pharmacogenomics. Accessed 8 Apr. 2017.

"Frequently Asked Questions about Pharmacogenomics." National Human Genome Research Institute, 2 May 2016, www.genome.gov/27530645/faq-about-pharmacogenomics/. Accessed 8 Apr. 2017

Help Me Understand Genetics: Genomic Research. US National Library of Medicine, 2018. Genetics Home Reference, ghr.nlm.nih.gov/primer/genomicresearch.pdf. Accessed 28 Sept. 2018.

Lam, Yui-Wing Francis, and Larisa H. Cavallari. Pharmacogenomics: Challenges and Opportunities in Therapeutic Implementation. Academic Press, 2013.

Licinio, Julio, and Ma-Li Wong. Pharmacogenomics: The Search for Individualized Therapies. John Wiley & Sons, 2009.

"What Is Pharmacogenomics?" Genetics Home Reference, ghr.nlm.nih.gov/primer/genomicresearch/pharmacogenomics. Accessed 8 Apr. 2017

Zdanowicz, Martin M. Concepts in Pharmacogenomics. American Society of Health-System Pharmacists, 2010.