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Pharmacogenomics: When drug treatment becomes personalized medicine
What are some of the barriers to using pharmacogenomics?
The field of pharmacogenomics is still in its early stages. It's possible that millions of genetic variations may exist, and identifying them all could take many years — if it's even possible. In addition, how you respond to a medication may not be determined by just one gene but rather by many genes interacting with each other. Combing through this complicated genetic map is expensive and time-consuming.
What types of personalized medicine are in use today?
Some types of personalized medicine based on the science of pharmacogenomics are in use today but on a limited basis. A few tests are now available that can help predict likely responses or bad reactions to certain medications.
Some of the tests available include:
- Cytochrome P450 genotyping test. A group of enzymes known as cytochrome P450 (CYP450) enzymes are responsible for metabolizing more than 30 types of medications and thus determine how quickly and effectively these medications are eliminated from your body. Because of your genetic makeup, your body may not break down the medications fast enough, instead allowing them to accumulate to levels that can result in severe side effects. Or, you may have a genetic variation that makes your body break down the medications too quickly, before they have a chance to work. The CYP450 test can be used to determine dosing and effect of certain antidepressant medications, anticoagulants such as warfarin, proton pump inhibitors and a number of other medications.
- Thiopurine methyltransferase test. An enzyme called thiopurine methyltransferase (TPMT) breaks down a type of chemotherapy drug called thiopurine that's used to treat some leukemias and autoimmune disorders. Some people have genetic variations that prevent them from producing this enzyme. As a result, thiopurine levels can build up in the body, leading to severe toxic reactions. A blood test can check for this genetic variation before treatment begins, giving doctors better dosing guidelines.
- UGT1A1 TA repeat genotype test. This test, commonly known as the UGT1A1 test, detects a variation in a gene that affects the UGT1A1 enzyme. This enzyme determines how the body breaks down irinotecan (Camptosar), a chemotherapy drug used to treat colorectal cancer. Some people have a deficiency in this enzyme, allowing the medication to build up to toxic levels and possibly causing suppression of the bone marrow, infection and even death. Doctors can test for this genetic variation before treatment starts and then customize the dosage to prevent a toxic buildup of the drug. On the flip side, if someone has normal levels of the UGT1A1 enzyme, the test may help doctors ensure that the dosage of irinotecan isn't lower than necessary.
- Dihydropyrimidine dehydrogenase test. The medication 5-fluorouracil (5-FU) including its related compounds is one of the most commonly used chemotherapy medications. Some people have a genetic variation that results in a decrease in the dihydropyrimidine dehydrogenase enzyme, which is responsible for breaking down 5-FU. As a result of this deficiency, some people may develop severe or even fatal reactions to 5-FU. Knowing ahead of time who has this deficiency can help doctors tailor the medication dosage to prevent these kinds of dangerous adverse reactions.
Where does the science of pharmacogenomics stand now?
In the future, pharmacogenomics could have an expanding role in the practice of medicine. But despite the promise of personalized medicine, pharmacogenomic testing is not widely available today. You should be skeptical of news reports and other sources of information proclaiming that pharmacogenomics or other types of personalized medicine will offer revolutionary results today. It is hoped that this will be true sometime in the future.
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