Pharmacogenomics: Tailoring Drug Therapies Based on Genetic Makeup

While effective at fighting disease, traditional medication can vary in effectiveness from patient to patient depending on factors such as individual differences in genetic makeup and metabolism rates, drug-drug interactions, and physiological responses.

In recent years, the field of personalized medicine has emerged to address this issue with several approaches, such as functional medicine and targeted drug therapy.

Pharmacogenomics is another personalized medicine approach that has seen significant research interest over the past few years, which studies how a patient’s genes influence drug response.

​​​​​​​Image Credit: Katy Pack/Shutterstock.comImage Credit: Katy Pack/Shutterstock.com

Using Precision Medicine: The Power of Pharmacogenomics

Inter-individual drug response variability is a common problem globally, with an increasingly elderly population likely to only cause this critical issue to grow.

Understanding how a patient’s genetic makeup and genomic factors influence several factors that affect this inter-individual variability is therefore vital for designing safe and efficacious therapeutics.1,2,3

Genes profoundly affect how well medications work. Enzymes, for instance, which are encoded by genes, have countless functions.

One function of enzymes is the breakdown of organic and synthetic molecules such as drugs. Variability in the breakdown rate of drugs can be due to genetic differences that change how well an enzyme works or the amount of enzyme produced.1

As explained above, Pharmacogenomics seeks to understand how these genetic differences can affect drugs' and therapeutics' absorption, efficaciousness, breakdown, and safety.

If a drug breaks down too quickly or slowly, for example, a typical dose will not work as expected. By understanding the underlying genetic basis of this drug response, pharmacogenomics aims to provide precision medicine capabilities.

There are a number of benefits when using a pharmacogenomics approach. These include improved drug safety, targeted drug development, improved efficiency, and reduced overall healthcare costs.

By understanding which variations occur within patients, healthcare providers can prescribe the most beneficial medications and safest drugs and discover new medications that can directly target gene variants.1

Read More About Personalized Medicine

Decoding DNA for Better Treatment: Pharmacogenomic Testing

The decreasing cost and better availability of genotyping technologies have led to increased focus on implementing the field of pharmacogenomics in several countries.

Blood samples or buccal (cheek) swabs are sent to a laboratory for pharmacogenomic testing.

Once in the lab, scientists employ several well-established genetic testing techniques, such as gene sequencing, bioinformatics, gene mapping, and DNA microarrays, to test the sample.4 This allows providers to select the most appropriate drug type and dose.

From Research to Reality: The Current State of Pharmacogenomics

Pharmacogenomic testing is well-established in oncology to test for inherited (germline) and acquired (somatic) genetic variants.

Several drug-gene pairs have been identified by pharmacogenomic studies, which are used for personalized medicine in a number of medical conditions, such as cancer, and psychiatric conditions, such as depression.3

A number of enzymes are already known to affect the metabolism and efficaciousness of several common medications.

Pharmacogenomic testing is routinely used for fluoropyrimidines, which are anti-cancer drugs, to ensure their safe and efficacious dose. A liver enzyme encoded by the gene DYPD can cause impaired fluoropyrimidine metabolism, leading to severe adverse drug reactions.3

Whilst the availability of pharmacogenomic testing is accelerating, and the field is already well established for a small number of specific types of drug-gene pairing and medical and psychiatric conditions, it is not yet standard for all medications.

Two main organizations, the Clinical Pharmacogenetics Implementation Consortium, and the Dutch Pharmacogenetics Working Group, have released guidelines over the past few years in an attempt to garner international consensus.

Other organizations include Ubiquitous Pharmacogenomics, the University of Chicago Center for Personalized Therapeutics, and PharmGKB.

In the UK, NICE has produced draft guidance for treating post-ischaemic stroke patients with antiplatelet therapy.

Pharmacogenomic studies have indicated that the enzyme CYPC219 plays a role in this condition, although pharmacogenomic testing for this is not commonplace in the UK at the moment.3

Challenges and Considerations

Like any scientific field, pharmacogenomics studies are guided by some key challenges and considerations. Moving pharmacogenomic techniques from the research lab to widespread clinical practice is daunting.

Firstly, there are technical challenges with personalizing medicine using a pharmacogenomics approach.

The genetic basis of inter-individual drug action variability is a highly complex subject that requires identifying factors such as the optimal patient subpopulation and developing rapid, efficient, and practical methods that determine specific individuals’ genetic makeups.

Furthermore, there are ethical, moral, and legal considerations. For example, there is the question of which individuals and stakeholders have access to sensitive medical information, data security, the privacy of personal genetic information, and how that information should be used.

Also, there is the question of equitability and the availability of personalized medicine, especially in locales where universal free healthcare is not available.

Large numbers of patients who would benefit from tailored drugs and pharmacogenomics research may not have the financial means. Alternative treatment options must be considered.

Finally, there may be an increase in orphan drug applications, which could cause a challenge for regulatory bodies. 4

The Future of Personalized Medicine: A Brighter Outlook

Despite the technical, legal, moral, ethical, and regulatory challenges associated with pharmacogenomics, the field holds huge promise for tailoring drugs to treat several ailments based on the genetic basis of inter-patient drug efficaciousness variability.

Personalized medicine holds the potential to be one of the 21st-century's most significant medical developments. It could improve health outcomes for millions of patients worldwide every year and prevent large numbers of otherwise preventable deaths. Pharmacogenomics can play a huge role in this.

References

[1] Cleveland Clinic (2023) Pharmacogenomics [online] Available at: https://my.clevelandclinic.org/health/articles/pharmacogenomics (Accessed on 5 June 2024)

[2] Pirmohamed, M (2023) Pharmacogenomics: current status and future perspectives Nature Reviews Genetics 24 pp. 350 – 362 [online] Nature.com. Available at: https://www.nature.com/articles/s41576-022-00572-8 (Accessed on 5 June 2024)

[3] Jennings, B & McDermott, J (2023) Introduction to pharmacogenomics [online] NHS England. Available at: https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/introduction-to-pharmacogenomics/ (Accessed on 5 June 2024)

[4] Ghosh, R, Ghosh, S & Chawla, S (2010) Pharmacogenomics: Practice and Challenges [online, Pdf] Racp.org. Available at: https://www.racgp.org.au/getattachment/9d642897-93ad-4d6c-972a-8c6255d33f33/Pharmacogenomics.aspx (Accessed on 6 June 2024)

Further Reading 

Last Updated: Jun 25, 2024

Reginald Davey

Written by

Reginald Davey

Reg Davey is a freelance copywriter and editor based in Nottingham in the United Kingdom. Writing for AZoNetwork represents the coming together of various interests and fields he has been interested and involved in over the years, including Microbiology, Biomedical Sciences, and Environmental Science.

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