"One size fits all" medications may soon be a thing of the past. The science of pharmacogenics holds the promise that one day medications might be tailor-made to a patient's unique genetic profile.
Have you ever wondered why a medication your doctor has prescribed -- for example, a diuretic -- turns out to have little effect on you, while a friend taking the same medication experiences a dramatic benefit? Or perhaps you’ve had an adverse reaction to a medication that most other people can take without difficulty. The “typical” effects a medication produces are established through research and clinical use. But this knowledge is based on the reactions of large numbers of patients. Individual responses to a medication may vary widely. The only sure way to know how you will respond to a specific medication is to try it -- and wait.
But what if you and your doctor could tell in advance how you will respond -- and choose a medication accordingly? A new science, known as pharmacogenomics, may soon make this possible. Its goal is to identify small, individual genetic differences -- or variants -- that lie at the root of differing drug responses. This information could then be used to select appropriate medication -- an advance so important that the U.S. Food and Drug Administration issued new guidelines urging drug companies to conduct pharmacogenomic tests as they develop new medications.
The genetic variants that account for some drug responses are already known and, in a few instances, tests for them are available. Scientists are tracking down the genetic basis for many others. Once they do, more tests are likely to follow. "Eventually, everyone will have his or her own drug profile," says Frank Giardiello, M.D., Professor and Chief of Gastroenterology at Johns Hopkins. "We’ll know which medication to prescribe, and whether we should give you more or less of the medication based on your unique genetic makeup."
Pharmacogenomic testing is especially important in cancer treatment because, although many medications are available, each medication is effective in only a certain percentage of patients. Selecting the most appropriate initial treatment can be critical, even lifesaving, in some cases. Women with breast cancer are already benefiting from advances in pharmacogenomics. The biologic therapy Herceptin (trastuzumab) is effective in breast cancer patients who carry a particular genetic marker called HER2, which is present in about 25% to 30% of patients. Doctors now routinely test patients for this marker to determine whether they are candidates for Herceptin.
Pharmacogenomics may also have a significant impact on the treatment of heart disease. A study published in the Journal of the American Medical Association (JAMA) examined the effect of diuretic therapy on the risk of heart attack and stroke in more than 1,000 patients treated for high blood pressure. It found that people with a particular gene variant that causes their kidneys to retain more salt responded better to diuretic therapy for high blood pressure than to other antihypertensive drugs. About one third of people with high blood pressure carry this particular variant, and in these individuals, diuretic therapy cut the risk of having a stroke or heart attack by half compared with other blood pressure medications. Diuretic therapy had no impact on the incidence of heart attacks and strokes in patients who did not carry this gene variant. Similarly, it appears that genetic differences may affect individual response to cholesterol-lowering statin medications. In a study reported in the Journal of the American College of Cardiology, German researchers identified a genetic variant that determines which patients will experience a long-term clinical benefit from statin therapy.
Avoiding serious, and potentially lethal, drug reactions is another goal of pharmacogenomics. Many of the gene variants linked to adverse drug reactions involve cytochrome p450 enzymes, an enzyme system responsible for a major portion of drug metabolism in humans. An estimated 7% of Americans lack certain p450 enzymes and thus are at risk for toxic reactions to drugs processed by these enzymes. Other people have variants of the enzymes that work so rapidly that they clear the drugs from the body before they have time to work. When tests to identify these p450 variants become more widely available, doctors will use them to better predict your response to a particular drug. Genetic variants have been identified in the principal enzyme that metabolizes the anticoagulant drug warfarin. Certain combinations of these genetic variants have been found to result in increased risk of bleeding complications. Eventually, screening for these genetic variants may allow doctors to adjust the dose of warfarin and reduce the risk of adverse reactions in people receiving the medication.
Several problems must be addressed before medications can be prescribed based on genetic makeup. First, the task of identifying the numerous genes that are likely to be involved is complex and will take time. In addition, some drug companies may be reluctant to conduct the necessary research because the process is costly and may decrease the market for their medications. If, however, genetic tests are used to select those patients for clinical trials who are most likely to be helped by the medication under development, the trials could proceed more rapidly, thereby cutting down on costs. In addition, by determining in advance which patients are most likely to benefit from a particular medication, pharmacogenomic testing could enable drug companies to bring products to market even if they help only a small number of people with a particular condition.
