Magazine article Drug Topics

Progress Continues on Selecting Best Drugs for Patients

Magazine article Drug Topics

Progress Continues on Selecting Best Drugs for Patients

Article excerpt

The science of pharmacogenomics is becoming an increasingly useful tool for predicting individual patient response to drug therapy, according to William E. Evans, Pharm.D., FCP, deputy director of St Jude Children's Research Hospital.

"Even when multiple polymorphisms are involved, it is possible to find a panel of diagnostics that can predict response to medication," Evans said. He was the keynote speaker at the annual meeting of the American College of Clinical Pharmacology, held recently in San Francisco. In a paper published in The Lancet in 2000, for instance, researchers found that six polymorphisms in four genes could predict the response of schizophrenic patients to clozapine with 75% accuracy.

Evans' own research on children with leukemia has revealed that gene expression profiling can be a powerful diagnostic and treatment tool. In a study of 350 children with leukemia, published in Cancer Cell in March of 2002, his team of researchers found that overexpression or down-regulation of certain genes predicted with 97% accuracy which patients would continue in remission or relapse. "This type of diagnostic tool has great potential in helping us select cancer therapy-- and identifying patients who need more intensive therapy," he said.

Evans' research group has also analyzed how genes change in response to cancer treatments. In the study of 350 children, participants were randomized to one of four common medications for leukemia, and changes in 13,000 human genes were monitored before and after treatment. The group found that there were unique changes in 124 of the genes they analyzed.

"Our current technology allows us to look inside medications and see what they're doing," Evans told the audience. "What we now want to know is whether these changes in gene expression forecast response." The answer is they do. In a study not yet published, Evans and his colleagues looked at 60 children with leukemia randomized to methotrexate and found that changes in expression in 87 genes right after treatment predicted who would stay in remission or relapse, even years later. "These are small numbers, but the data are very provocative," he said. "It reveals to us which genes are involved in polymorphism."

Such knowledge is especially useful because the empirical approach to prescribing drugs often doesn't work "By giving the same medication at the same dose to different patients, we don't take into account individual differences," Evans said. …

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