Personalized medicine: Tailoring treatment to your genetic profile

Gene variations are common but can have a big impact on how your body processes medications. See what genetic tests are available to help customize your treatment.

In medicine, one size doesn't fit all. Two people who take the same cancer medication, for instance, may have very different responses. One may have severe, even life-threatening side effects, while the other experiences few if any side effects and seems to sail through treatment. Or, the drug may shrink a tumor in one person but not in another.

How could two people have such drastically different reactions to the same medication? Chalk it up to genes. People inherit variations in their genes. And even slight variations can have a profound effect on how your body responds to certain medications.

Today, a handful of tests are available that can detect some of these genetic variations and predict how you're likely to respond to certain medications. Doctors are already using some of these tests to help customize treatment based on a person's specific genetic variations, particularly in the area of cancer. This practice is called personalized medicine. Here's a closer look at personalized medicine, how it's applied today and what the future may hold.

What is personalized medicine?

Personalized medicine is known scientifically as pharmacogenomics or pharmacogenetics. Pharmacogenomics is the study of how inherited variations in an individual's genes affect how his or her body processes and responds to medications. Pharmacogenomics is a combination of pharmacology and genomics — drugs and genes.

How do genes influence response to medications?

Genes are segments of DNA, which is found in all of your cells. DNA is essentially a chemical database for your body, instructing it how to behave and interact on a cellular level. A basic gene can have many different forms. For instance, consider the gene that determines hair color. Normal variations of that gene determine specific hair color, such as brown or blond.

Similarly, your genes determine how complex chemical reactions play out within your body. A particular gene may dictate how your body processes (metabolizes) a certain medication. Some people might have a slight variation in that particular gene. As with the hair color gene, the variation in this gene is perfectly normal. But just as you may end up with a different hair color, you also may end up reacting differently to a medication if you have that genetic variation. You may have a variation that makes the drug stay in your body longer than normal, causing serious side effects. Or you may have a variation that makes the medication less potent, for instance.

Scientists are trying to identify and record as many genetic variations as possible. Once a variation is identified, scientists can match it up with a response to a particular medication and then develop a personalized approach to medicine.

How does personalized medicine work?

Say you're diagnosed with a certain disease for which you must take medication, such as breast cancer. You and your doctor choose a medication based on standard medication and dosing guidelines for that disease. Your doctor may also take into account such factors as your weight, age, medical history and even how any blood relatives have reacted to the same medication. Despite all of that, neither you nor your doctor knows how you'll actually react to the medication. You may experience terrible side effects — or none at all. The medication may help your cancer — or it may have no effect. Consequently, you may have to return to your doctor many times to adjust the dosage or to switch medications. This is how medication choices generally work today — it's often a matter of trial and error.

With the advent of personalized medicine, however, that process is beginning to change. Before you take a single dose of medication, you may be able to have a blood test to see which genetic variations you have. The test may show that you have a variation that's likely to adversely affect how you respond to the medication. So your doctor skips that drug and prescribes a different one. Or, your doctor alters the dose to match your body's genetics. Your unique genetic profile can help your doctor personalize your treatment.

What are the benefits of personalized medicine?

Personalized medicine has the potential to offer many benefits, if the emerging science becomes reality.

Some of the potential benefits include:

Making better medication choices. Each year, some 100,000 Americans die from adverse reactions to medications and more than 2 million are hospitalized. Medications generally undergo a rigorous review and testing process before being approved for sale. But until the dawn of pharmacogenomics, there was no way to predict how a certain individual would react to a drug. So even if a medication appears safe for most people, some people may have a toxic reaction to it because of variations in their genes. Pharmacogenomics may be able to predict who's likely to have a bad reaction to a drug before they ever take it. It may also be able to predict if you'll respond well to a medication — whether your breast tumor will shrink, for example.
Safer dosing options. As it stands now, the dosage of a medication is either a standard one-size-fits-all dose or it's based on factors such as your weight and age. That might not be good enough, though. A standard dose may prove toxic to one person and not another, because of their genetic variations. Personalized medicine may get around this problem by predicting which dose of medication is right for you, not just which particular medication is right. So you and your doctor may spend less time trying out various dosages to find one that works well, with the fewest side effects and most benefits for your condition.
Improvements in drug development. Pharmaceutical companies often must spend years conducting research and clinical trials for a new drug before it goes to market. They have to test a drug in many people to ensure that it's safe and effective. Pharmacogenomics may help these companies better focus their drug testing. If companies know ahead of time that someone has a genetic variation that will cause a bad reaction to the drug or that will make the drug ineffective, those people can be excluded from the clinical trial. This may speed up the clinical trial process and better target people who can be helped by a certain medication.
Decreased health care costs. Personalized medicine may be able to control health care costs in several ways. For one, it may be able to reduce the number of deaths and hospitalizations from adverse reactions to drugs. In addition, you may not have to spend a lot of money out of your own pocket trying medications that ultimately won't work for you. Finally, speeding up the clinical trial process can reduce the cost of developing drugs.

What are some of the barriers to personalized medicine?

The field of personalized medicine 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?

Personalized medicine is in use today but on a limited basis. Several tests are now available that can help predict likely responses or bad reactions to certain medications, and more are in development.

Here's a look at some of the more common tests available:

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 making sure they're effectively eliminated from your body. Certain genes are responsible for producing these CYP450 enzymes. These genes may contain variations that alter how your body metabolizes these medications. In some cases, 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 for certain antidepressant medications, anticoagulants, proton pump inhibitors and many other medications.

This test may also be valuable for people who take certain antidepressants at the same time that they're taking tamoxifen (Nolvadex) for breast cancer. A series of studies has shown that genetic variations in a certain type of CYP450 enzyme, called CYP2D6, may be important in how people respond to tamoxifen. These variations may make some people have a poorer response to tamoxifen. Having this information in advance can help doctors customize medication dosage to an individual.

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. 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 variation before treatment starts and then customize the dosage to prevent a toxic build up 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) and 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 personalized medicine stand now?

As scientists learn more about individual genetic variations, the potential of personalized medicine grows. Although many of the first pharmacogenomic tests to check for genetic variations were most useful in alerting doctors about the likelihood of a severe adverse reaction to a drug, there are a growing number of tests being developed to determine whether someone will respond to a particular medication. That is, the tests may be able to predict if a medication will actually help improve their condition, such as shrinking a tumor. Tamoxifen is one example, and new research indicates that a pharmacogenomics test under development may be able to predict how some people respond to the lung cancer drug gefitinib (Iressa).

Despite the promise of personalized medicine, pharmacogenomics testing is not widely available. Some doctors who aren't yet aware of its value may not routinely use these tests in their practice. These tests may also be expensive, and your health insurance plan may not cover their costs.