Precision medicine and pharmacogenomics
Modern medications save millions of lives a year. Yet any one medication might not work for you, even if it works for other people. Or it might cause severe side effects for you but not for someone else.
Your age, lifestyle and health all influence your response to medications. But so do your genes. Pharmacogenomics is the study of how a person's unique genetic makeup (genome) influences his or her response to medications.
What is precision medicine?
Precision medicine aims to customize health care, with decisions and treatments tailored to each individual in every way possible. Pharmacogenomics is part of precision medicine.
Although genomic testing is still a relatively new development in drug treatment, this field is rapidly expanding. Currently, more than 200 drugs have label information regarding pharmacogenomic biomarkers — some measurable or identifiable genetic information that can be used to individualize the use of a drug.
Why is genomic information helpful?
Each gene provides the blueprint for the production of a certain protein in the body. A particular protein may have an important role in drug treatment for one of several reasons, including the following:
- The protein plays a role in breaking down the drug.
- It helps with the absorption or transport of the drug.
- The protein is the target of the drug.
- It has some role in a series of molecular events triggered by the drug.
When researchers compare the genomes of people taking the same drug, they may discover that a set of people who share a certain genetic variation also share a common treatment response, such as:
- A greater risk of side effects
- The need for a higher dose to achieve a therapeutic effect
- No benefit from the treatment
- A greater or more likely benefit from the treatment
- The optimal duration of treatment
This kind of treatment information is currently used to improve the selection and dosage of drugs to treat a wide range of conditions, including cardiovascular disease, lung disease, HIV infection, cancer, arthritis, high cholesterol and depression.
In cancer treatments, there are two genomes that may influence prescribing decisions — the genome of the person with cancer (the germline genome) and the genome of the cancerous (malignant) tumor (the somatic genome).
There are many causes of cancer, but most cancers are associated with damaged DNA that allows cells to grow unchecked. The "incorrect" genetic material of the unchecked growth — the malignant tumor — is really a separate genome that may provide clues for treatment.
How does pharmacogenomics work in practice?
One example is thiopurine methyltransferase (TPMT) testing for people who are candidates for thiopurine drug therapy. Thiopurine drugs are used to treat some autoimmune disorders, including Crohn's disease and rheumatoid arthritis, as well as some types of cancer, such as childhood leukemia.
The TPMT enzyme helps break down thiopurine drugs. People who are TPMT deficient don't break down and clear out these drugs quickly enough. As a result, the drug concentration in the body is too high and increases the risk of side effects, such as damage to the bone marrow (hematopoietic toxicity).
Genetic testing can identify people with TPMT deficiency so that their doctors can take steps to reduce the risk of serious side effects — by prescribing lower than usual doses of thiopurine drugs or by using other drugs instead.
The future of pharmacogenomics
Although pharmacogenomics has great promise and has made important strides in recent years, it's still in its early stages. Clinical trials are needed not only to identify links between genes and treatment outcomes but also to confirm initial findings, clarify the meaning of these associations and translate them into prescribing guidelines.
Nonetheless, progress in this field points toward a time when pharmacogenomics will be part of routine medical care — at least for some drugs.
Last Updated Sep 3, 2020