The Diagnostic Dilemma

Doctors will soon have an arsenal of new genetic tests to help select the appropriate treatments or drugs for patients. Will they know how to use them?

In the last year, several new genetic diagnostic tests have hit the market: two tests that can predict from a person's genes how well he or she will metabolize certain drugs and a third that forecasts whether lung cancer patients will respond to a specific treatment.

The tests herald the arrival of personalized medicine, which will allow doctors to select treatments and optimize drug doses for individual patients. But, according to many physicians and researchers, such tests alone won't be much help. Rather, doctors will need to learn how to incorporate them into their clinical practices, and scientists will have to figure out what kind of guidelines doctors need to do this properly.

"We need to provide enough context that the average doctor in Idaho can look at the labeling [on a drug that can be genetically targeted] and understand and truly know what to do," says Wayne Rosenkrans, director of scientific and medical strategy at AstraZeneca Pharmaceuticals in Wilmington, DE.

Tarceva, a drug for lung cancer, and its accompanying diagnostic test are often hailed as a model for this intersection of genetics and pharmacology, called pharmacogenomics. In May 2004, scientists discovered a mutation in the gene for the epidermal growth factor receptor (EGFR) that predicts who will respond to the drug. (The drug is more effective in patients whose tumors carry the mutation.) Sixteen months later, in September 2005, a commercially available version of the test was on the market, made by Genzyme Genetics, a diagnostics company based in Westborough, MA.

Doctors can use the Genzyme test to help select the right treatment for a patient -- but the results aren't always black or white, for not all patients who respond well to Tarceva carry the EGFR mutation. "Biological complexity strikes again," says Rosenkrans. "If you want an effective diagnostic, you can’t just look at the EGFR receptor."

Lecia Sequist, an oncologist at Massachusetts General Hospital and part of the team that identified the EGFR mutation, is running clinical trials on use of the diagnostic test in the clinic. "When [the mutation] was first discovered, it seemed very exciting -- like a simple answer you could give doctors about who would benefit," she says. But as more and more data came in, scientists discovered other factors that also affect how well Tarceva works, such as extra copies of the EGFR gene. "The test is useful, but we're still trying to figure out the best way to use it," says Sequist. Genzyme is now developing a new test to identify extra copies of the EGFR gene.