January 21, 2005

Improving drug therapy all in the genes: speaker

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William Evans, Pharm.D.

Improving drug therapy all in the genes: speaker

Scientists must prove the value of genetic testing before it will be widely applied to improve drug therapy, a leading researcher said this week.

William E. Evans, Pharm.D., director and chief executive officer of St. Jude Children's Research Hospital in Memphis, is internationally known for his contributions to the treatment of childhood cancer and to pharmacogenomics, which aims to determine why individuals respond differently to drugs.

On Tuesday, as the first Grant R. Wilkinson Distinguished Lecturer in Clinical Pharmacology at Vanderbilt University Medical Center, Evans described the potential of pharmacogenomics to improve the efficacy of drug therapy, avoid side effects and ultimately to increase survival.

Better understanding of polymorphisms, or slight genetic differences in the body's ability to metabolize, or break down drugs, can help doctors determine the proper dose of a drug in order to maximize effectiveness and minimize drug-related complications in individual patients.

Similarly, understanding the genetic characteristics of acute lymphoblastic leukemia (ALL), the most common form of cancer in children, has enabled doctors to choose drugs that are most likely to kill tumor cells.

The results of these and other advances have been nearly a tenfold increase in the cure rate for ALL during the past 40 years, from less than 9 percent in the 1960s to more than 80 percent in 2002, Evans said.

“There hasn't been a new drug (for the disease) in the last 20 years,” he said. “We've seen survival increase simply by using older drugs in a smarter fashion.”

Yet genetic testing continues to be sporadic, even when considerable and increasing scientific evidence indicates that such testing would benefit patients.

“The burden is on us at academic medical centers to begin to not only provide … evidence that these genetic polymorphisms are influencing significantly the drug response … but to begin to incorporate that into treatment plans and protocols and to show … that it actually makes a difference,” Evans said.

It won't be easy. Most drug effects probably result from the complex interactions of several genes, and scientists must understand those interactions before they can figure out how to accentuate a desired drug effect or extinguish an undesired one. “That is a daunting challenge,” he concluded, “but one which is certainly doable.”

The endowed Wilkinson lectureship was established this month to honor the contributions of Grant R. Wilkinson, Ph.D., D.Sc., professor of Pharmacology at Vanderbilt, whose papers are among the most frequently cited by pharmacologists worldwide.

Private and corporate sponsors, including many of Wilkinson's colleagues at Vanderbilt and around the world, contributed to the endowment, which will support an annual lecture by a world-class authority in Clinical Pharmacology, drug metabolism, pharmacokinetics or pharmacogenetics.

“It's a tribute to an icon,” Evans said, “one who's had a tremendous impact on my career.”

In brief remarks to colleagues and students who packed the Light Hall lecture hall, Wilkinson, in characteristic modesty and wit, said, “To be quite honest, I don't deserve this honor. But I have arthritis. I don't deserve that either.”