Pharmacogenetic testing (pgx) is the process of testing an individual’s genes to determine how the body responds to medications. The term comes from the words “pharmaceutical” and “genetic.” The idea of pharmacogenetics is not new, as Friedrich Vogel coined this term in 1959. Pharmacogenetics considers individual responses to drugs at the genetic level and is also called pharmacogenomics.
DNA or deoxyribonucleic acid is the genetic material-carrying molecule inside the cells of living organisms. Genetic material determines how an organism develops and operates. Parents pass DNA characteristics to their offspring, and this is known as heredity. DNA plays a role in how each person’s body metabolizes drugs. In DNA testing for medication, a DNA swab of a patient’s cheek is taken and sent to a lab for processing to determine how quickly and effectively the body may process or respond to medications.
Pharmacogenetics or drug gene testing studies the genetic differences in drug-metabolizing genes. Metabolization is the process of breaking down drugs so the body can use them to fight disease. Some of the questions that pharmacogenetics may be able to answer for medical practitioners include: “Why is this drug not working for my patient?” and “Why is my patient having severe side effects when others can tolerate this medication without issues?” When doctors treat patients with successive medications and nothing seems to work, genetic testing for medication effectiveness may provide guidance that will help the clinician prescribe treatment based on a patient’s genetic makeup and medical history. Pharmacogenetic test results can help doctors prescribe medications that work when standard therapies fail.
Cytochrome P450 (CYP450) is an example of an enzyme that helps the body metabolize drugs. Specific genes encode this and other drug-metabolizing enzymes and help them break down medications, enabling the body to fight diseases. However, due to genetic variations, medication can be effective for one person and ineffective for another. A drug that causes no issues for one person might have devastating side effects for another. Low enzymatic activity may prevent a patient from metabolizing medications like antidepressants and antipsychotics. When the drugs remain in the system too long, they can cause serious side effects. In contrast, in those with high levels of enzymatic activity, medications can break down too quickly, putting patients at risk because the medicine does not remain in the system long enough to affect the condition.
Pharmacogenetics testing helps doctors pinpoint how well the body uses medications, allowing them to personalize prescriptions based on how they will help the patient. This practice is sometimes called precision medicine and is a way of customizing treatments that can help them work more effectively. Pharmacogenetics testing plays a role in precision treatments.
Due to pharmacogenetics testing and research, there are now drugs labeled with genetic information that can help clinicians practice precision medicine. Researchers compare the genetic material of individuals taking the same medication by studying groups of people with similar genetic variations. Researchers can look for common responses to treatment, such as increased dosage, a higher risk of side effects, expected or better response to treatment, the length of time needed to achieve good treatment outcomes, and no positive results from the treatment. Individuals who have arthritis, heart disease, cancer, HIV, and other conditions have been beneficiaries of such research. In many cases, pharmacogenetic research has enabled health care providers to prescribe successful treatment based on genetic markers.
One of the questions that puzzle health care providers, especially those who treat cancer, is why some drugs work better for some patients but have no effect in others with the same cancers. Many cancer medications must be “switched on” to work. This turning on of a drug is known as activation, which is facilitated by enzymes. If the enzymes do not respond, the therapy will not be effective in fighting cancer.
The same chemotherapy prescribed for two breast cancer patients may work for one but be ineffective in another. The Breast Cancer Genome-Guided Therapy Studies (BEAUTY studies) are examples of research that is guiding how clinicians use pharmacogenetic testing to develop individualized therapies based on the patient’s test results.
As a result of what experts have learned in these studies, treatment based on pharmacogenetics shows promise for breast cancer patients who experience residual cancer after going through standard chemotherapy. Individuals who suffer from other cancers, including colon cancer, leukemia, and pancreatic cancer, who have lower levels of certain metabolizing enzymes can benefit from lower doses of chemotherapy. As a result, they may experience fewer side effects.
Not only is it necessary to look at genetic variations in the individual who has cancer, but tumors can also pose problems due to genetic variations. Malignant tumors can arise from damaged DNA encouraged rapid cancer cell growth. Understanding the genetics of the tumor can provide some insight into the best way to treat it.
The inability to tolerate certain medications can leave some patients struggling with pain management, misusing drugs, and stopping medications because of undesirable side effects. When a patient is on a medication that causes stomach upset, the symptoms can interfere with work and home life. As a result, the patient might decide to stop using the medicine, which can be more dangerous than the uncomfortable symptoms. Through pharmacogenetics testing, the doctor might find that a lower dose of the medication can treat the patient without the undesirable side effects. Likewise, if a patient is taking pain medicine and getting little relief, the tendency on the patient’s part is to increase the dosage in hopes that more is better. However, this can lead to toxic levels of the drug in the body and overdosing.
The failure of the drug to provide the needed relief might be in how the body metabolizes it. If that process is too quick, the dose may not be effective; however, the patient’s doctor, not the patient, needs to adjust the medication. Knowing whether a patient has a genetic predisposition to rapid medication metabolism can help the doctor practice precise dosing. For individuals requiring pain relief, getting effective, safe, and targeted treatment for pain may help reduce the risk of overdoses associated with opioids.
When prescribing medications for patients, doctors take several factors into account, including age, history, existing medical issues, lifestyle, weight, height, sex, and how a new drug may interact with current medications. However, what the doctor cannot assess without Pgx testing are the unique genetic factors that can lead to adverse drug reactions. Genetic variations that prevent the body from metabolizing a medication can result in a patient having a response that can lead to debilitating illness and death. For example, medication may build up in the body, be too strong for a patient, and lead to death. One way to reduce the risk of adverse drug reactions is to have patients get a pgx test before prescribing medication.
Unless they see a doctor who routinely orders pharmacogenetics testing, many people are unaware of the potential benefits. Patients who are not seeing the desired outcomes from prescribed therapies can start the conversation by asking their health care providers if genetics could play a role.
Imagine a world where a patient visits a health care provider with a complaint, and pharmacogenetics testing is routine. In this scenario, the doctor would order pharmacogenetics testing with other lab tests, and the resulting report could provide a road map for treatment based on the patient’s genetics. Pharmacogenetics testing is not the norm in most medical practices, but with more research and positive outcomes, that could change. Treatments that take genetic variations into account could become standard practice.