The Evolution of Pharmacogenomics

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Drug Topics Journal, Drug Topics July 2021, Volume 165, Issue 7

Pharmacogenomics provides an opportunity for pharmacists to enhance their role in patient care.

At one point in our education, we all learned about Watson and Crick discovering the double helix structure of DNA in the 1950s. Although Watson and Crick did not know it at the time, this groundbreaking discovery would be the start of evaluating a patient’s specific DNA for more personalized pharmacological treatment.

After Watson and Crick’s discovery, there was a gold rush for DNA. Many new inventions and discoveries would follow years after. Half a century later, the Human Genome Project was launched in 1990 and completed in 2003.1 The goal of the Human Genome Project was to map and identify all of the human DNA base pairs and genes. Branching from the Human Genome Project is now the newer use of pharmacogenomics for medication therapy.

The first example of using DNA sequencing for disease treatment was the discovery of the human epidermal growth factor receptor 2 (HER2)-positive breast cancer mutation in the 1990s.2 Physicians were now able to screen for this HER2 mutation in patients with breast cancer. If the breast cancer expressed the protein HER2/neu, the patient would be receptive to trastuzumab (Herceptin), and therefore treatment would lead to a much better outcome. This proved to be a lifesaving discovery, and it inspired testing like this to continue.

Since then, testing for genetic variations has become a standard of practice in several areas of health care, including cancer, cystic fibrosis, and HIV. The cost per human genome continues to decrease with technological advancements and more data. Therefore, conducting this testing has become more standardized and less expensive (see Figure).3

Currently, pharmacogenomics testing is used for various pharmacokinetic and pharmacodynamic properties, mainly focused on the metabolism of different medicines. The pharmacogenomic results regarding metabolism express whether a patient will be predisposed to a lack of response due to a lower concentration of medicine, normal response, or toxicities from a higher concentration of medicine.

As developments in pharmacogenomics progressed over the years, several initiatives attempted to standardize pharmacogenomic medication information and guidelines. Because of this demand, the Pharmacogenomics Global Research Network and PharmGKB teamed up to develop a shared project termed the Clinical Pharmacogenetics Implementation Consortium (CPIC).4 CPIC addresses the need for guidelines to instruct clinicians on how to modify drug therapy based on genetic information. CPIC provides information on the proven genetic variations and the variations’ effects on medication therapy in 1 concise, clear guideline. CPIC information should be referred to and used by clinicians when applicable to select appropriate medications and doses for patients with genetic variations. As of this publication, there are over 40 medications with CPIC guidelines.

Optimizing Medication Use

Through CPIC and other sources of pharmacogenomic data, prescribers can now use this information to optimize medication therapies for patients. Genetic variations can cause a patient to have altered responses to medications. The common area where these genetic variations are seen is in the metabolism of the particular medication. If a patient metabolizes a medication for elimination at a slower rate than expected, the patient can be predisposed to toxic concentrations when given standard doses of the medication. Additionally, if a patient metabolizes a medication for elimination at a faster rate than expected, the patient can be predisposed to a subtherapeutic concentration of the medicine. The opposite of these responses will happen when the medication in question is a prodrug, which is an inactive medication metabolized to an active pharmacologic agent in the body, ie, faster metabolism = toxic concentration; slower metabolism = subtherapeutic concentration.

Medication therapy can be optimized when a patient’s DNA sequence is evaluated for known genetic variations associated with certain medications. Personalizing medication choices and doses to the specific needs of a patient’s genetic results will lead to the correct therapeutic drug concentrations while avoiding toxicities or subtherapeutic concentrations.

Pharmacogenomics can not only optimize therapy through proper dose and drug selection but also lead to optimization in other areas of health care. If a patient experiences toxicities leading to adverse effects (AEs) from a medication, they often have to receive additional care either through emergency services or through additional  medication to control the AEs. If pharmacogenomics is considered at the time of prescribing, the therapy can be optimized from the start and additional treatment can be avoided. This saves time for the patient and saves health care dollars overall.

The Role of the Pharmacist Across Care Settings

Today, pharmacists are the drug experts within the medical field, with extensive education in medication therapy including a heavy focus on pharmacokinetics and pharmacodynamics. Pharmacists have the knowledge and community presence to counsel patients about their genetic results, as well as educate other health care professionals. Through this education, pharmacists can help physicians make recommendations at the time of prescribing. These recommendations can include genetic testing to be done before new medication orders, as well as adjustments to be made on current medication orders.

Additionally, pharmacists can help address pharmacogenomic components as the last point of intervention before dispensing the medication to the patient. If a new prescription arrives for a patient with an established AE profile, the pharmacist may be the last person to verify if genetic testing has been done. Detrimental AEs can be avoided through intervention at this point in the prescribing process.

Furthermore, pharmacists can serve as advocates for this area of health care. The only way to collect data on additional genetic variations and their associations with medications is through clinical trials. There is a lack of financial incentive for pharmacogenomic clinical trials to be conducted and many clinicians do not understand the importance of this area of research. Pharmacists can encourage health care professionals to begin trials to expand their knowledge of pharmacogenomics and its application in health care.

The Future of Pharmacogenomics

Though pharmacogenomics in health care has come a long way from where it started, there is still a great deal of growth in this field and there are many more barriers to be crossed. One barrier in pharmacogenomics is the issue of where to store a patient’s genetic information. With genetic results being protected by the Health Insurance Portability and Accountability Act, it is hard to deter- mine an easily accessible place where genetic information can be seen and used by all parties within the health care system. A potential suggestion some physicians have made is an electronic health record pop-up alert on a patient’s profile at the point of prescribing, but development is still needed in this area.

In addition, there is an ethical component when testing a patient’s genetics. Scientists could come across a mutation the genetic test was not indicated for. This is a gray area to decide whether the patient should be informed of the findings since they did not originally consent to search for that mutation. There is also the question of testing for 1 specific gene variation vs testing a multigene panel on a patient. Once again, this is an area that needs more discussion and development.

As previously mentioned, clinical trials are imperative to the development and success of using pharmacogenomics in healthcare. There is no other way to get the information than to test a patient’s genes and evaluate them for their medication use. Pharmacists play a key role here in educating for clinical trial needs and advocating for more research. Overall, pharmacogenomics is an exciting and growing area of health care. Through additional research and a commitment to using pharmacogenomic findings, this information can eventually be brought to the bedside of every patient to optimize medication therapies for all.

1. The Human Genome Project. National Human Genome Research Institute. Updated December 22, 2020. Accessed June 3, 2021.

2. Cornez N, Piccart MJ. Cancer du sein et Herceptin [breast cancer and herceptin]. Bull Cancer. 2000;87(11):847-858.

3. DNA sequencing costs: data. National Human Genome Research Institute. Updated December 7, 2020. Accessed June 3, 2021.

4. What is CPIC? Clinical Pharmacogenetics Implementation Consortium. Updated April 21, 2021. Accessed June 3, 2021.

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