A series of advances are finally beginning to make personalized medicine a reality.

The Mayo Clinic this month introduced a genetic test that can tell colon-cancer patients if they are at increased risk of a toxic reaction to one of the primary front-line treatments for the disease.

In a separate study published this week in the Journal of Clinical Oncology, researchers identified a common genetic variant that appears to explain why some women with breast cancer are more likely to relapse while taking the widely used drug tamoxifen.

At the same time, the Food and Drug Administration is weighing action that could pave the way for widespread use of genetic tests that would help tell doctors how big a dose of the blood thinner warfarin to prescribe. Warfarin, taken by more than two million Americans to prevent blood clots, can have serious side effects if patients get too much or too little of the drug. The FDA has also been developing new regulatory guidelines for personalized medicines as it sees growing interest from drug makers looking at ties between genetic tests and how drugs work.

These developments are the latest in a series of steps forward in genetic knowledge that are poised to transform diagnosis and treatment of many diseases. Medicine is beginning to turn from a one-size-fits-all paradigm to a more personalized approach. The tests "allow physicians to think about patients as individuals," says Lawrence Lesko, director of the FDA's office of clinical pharmacology and biotherapeutics. Dr. Lesko oversees the agency's initiative to encourage use of genetic information in drug development.

In particular, genetic tests are likely to reduce adverse drug reactions, which by some estimates cause 100,000 deaths and two million hospital admissions each year in the U.S.

Until now, most genetic tests have simply determined whether a patient has or is at risk of an inherited disorder. Amniocentesis, for instance, enables pregnant women to screen a fetus for Down syndrome and other birth defects.

By contrast, the coming wave of "pharmacogenomic" tests detect genetic variations in the patient that affect how he or she responds to drugs. For instance, the new Mayo Clinic test determines whether patients have an genetic variation that increases their risk of a toxic reaction to the colon-cancer drug, called irinotecan, which can lead to diarrhea and life-threatening infection. A handful of other pharmacogenomics tests are on the market. A test known as TMPT, for example, checks for a genetic variation that puts patients at risk of toxicity to a leukemia drug and affects about 1 percent of such patients. It isn't known exactly how many new genetic tests are in development, but the Mayo Clinic currently sells six such tests to its customers, and it expects to add 12 more to its inventory next year.

The blood thinner warfarin, irinotecan and other chemotherapy drugs have what doctors call a narrow therapeutic window, where a dose that's a little too high can provoke serious side effects, while one a little too low provides little benefit. Genetic variability can influence a drug's effect. "We haven't been accounting for it," says Matthew Goetz, a Mayo Clinic oncologist. "Now we will account for it and it will help us individualize medicine in a better way."

To be sure, researchers caution that the strategy is just emerging and that broad availability of most such tests is likely at least five to 10 years away. Important questions -- including how to use results to guide treatment and whether insurers will pay for them -- need answering before doctors will adopt them as important tools for their patients.

"Everybody who buys a suit would like to have a tailor fashion it to their body," says Robert J. Mayer, director of the center for gastrointestinal oncology at the Dana Farber Cancer Institute in Boston. But "integrating such an approach reasonably into the care of patients at this point remains a bit of a challenge."

But already, the FDA is developing new regulatory guidelines for personalized medicines. A special FDA program that allows manufacturers to bring new data -- such as the results of genetic tests given to patients enrolled in drug trials -- to the agency for review and advice has gotten 25 responses. That's up from just six a year ago.

The agency is also preparing guidelines for companies that want to apply for joint approval of a drug and a related genetic test. And it is expected to issue a proposal on how to apply for approval of tests for inherited genetic markers, meaning genetic characteristics that a person gets from her parents, according to people with knowledge of the matter.

The Mayo Clinic's irinotecan test detects a variation in an enzyme called UGT1A1 that is involved in how the drug is metabolized by the body. About 10 percent of white Americans inherit two copies of a genetic variant -- one from each parent -- that inhibits metabolism of the drug and results in a much higher risk of a toxic reaction. A slightly different variation affects a similar amount of African-Americans, the clinic says. Many other patients have one copy of the variant that is also associated with a risk of toxic response, albeit a lower one.

The test, which the clinic has licensed from the University of Chicago, is being offered world-wide through the clinic's Mayo Medical Laboratories and has a list price of $680. Results are available within two to three days. A version is also available under a sublicense from Mayo through Third Wave Technologies, Madison, Wis.

What isn't clear is how doctors should use the test. "If I were to find my patient was at high risk of toxicity, there are no standard guidelines on what to do with the test results," Dr. Goetz says. The clinic is conducting a prospective study to evaluate potential alternatives. In addition to putting high-risk patients on lower doses of the drug or alternative treatments, it may turn out that people at low risk could benefit from a higher dose, he says.

About 145,000 new colon-cancer cases are diagnosed in the U.S. each year and nearly a million world-wide. Irinotecan, marketed as Camptosar by Pfizer Inc., is often used in a cocktail with other drugs in patients with advanced colon cancer.

Patients who take warfarin may be the next to have the option of genetic tests to guide treatment. Last month, an FDA advisory committee recommended that the agency put information about the tests into the label for warfarin, and the agency typically follows such committees' advice.

Warfarin is a complicated drug for doctors to prescribe. Patients are at risk of internal bleeding if they get too high a dose, or blood clots if they don't get enough. But scientists have found two genetic markers that help signal what dose to give a patient. Between them, they can affect the recommended dose by more than 50 percent -- reducing the typical starting dose from 5 milligrams to 2 mg, for instance. The new tests will be "an important option for patients beginning warfarin," says Brian Gage, associate professor at Washington University in St. Louis who is leading an National Institutes of Health-funded study of genetic markers for the drug.

PGxl Laboratories LLC, in Louisville, Ky., already sells a warfarin genetic test for $250, and hopes to add the other warfarin-related test early next year. The Mayo Clinic also sells a warfarin test and is conducting a study on how to use such tests to guide treatment.

Tailored Treatment

Genetic tests that can help personalize drug therapies:

A new test predicts side effects from colon-cancer drug irinotecan. FDA approved, commercially available.

A test predicts benefit from breast-cancer drug tamoxifen. Commercially available but needs further validation.

Tests for two different genetic variations that predict best dose of the blood-thinner warfarin. FDA weighing whether to include information in the drug's label about the link to the genetic variations.