Researchers looking for such connections confront an enormous hunting ground of approximately 33,000 human genes. Normally their only options for mounting a search in such a vast field are either to rely on anecdotal reports of dramatically altered patient reactions, or to conduct extensive surveys of the genes for all the proteins known to interact with a given drug.
The new approach lets nature and a robotic screening system do the majority of the hunting for them. In their initial test, which will be described in the August 10 Proceedings of the National Academy of Sciences, investigators rapidly found potential connections between two chemotherapy drugs and two regions of human DNA that contain approximately 100 genes each. The study is currently available online.
"This isn't the answer to everything in terms of finding these links, but it's an important breakthrough," says senior investigator Howard L. McLeod, PharmD., associate professor of medicine, genetics and of molecular biology and pharmacology. "This approach is very likely to allow us to find links between pharmaceuticals and genes that we never would have been able to anticipate."
McLeod is an expert in pharmacogenetics, a new field where scientists are learning that a person's genes can dramatically influence the effectiveness of medications. These differences can change a drug that is a lifesaver for some patients into a toxin for others, or influence whether a medication provides little benefit or is a remarkably effective treatment. By identifying genetic factors that affect patients' responses to drugs, scientists hope someday to enable clinicians to customize treatment plans.
McLeod and colleagues in the Division of Biostatistics took advantage of cell lines establish
Contact: Michael C. Purdy
Washington University School of Medicine