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Cancer drug side effect caused by cell 'pump' problem

people will help clinicians identify patients who should have their treatment modified by reducing the dose of the drug or switching to another one," she said.

The finding was made during a study of patients being treated with gefinitib for non-small cell lung cancer. The results suggest that other cancer drugs handled by the ABCG2 pump pose the threat of side effects to patients as well, according to Baker. She is the senior author of a report on this study that appears in the December 6 issue of the Journal of the National Cancer Institute.

"Gefitinib represents a new type of treatment called targeted therapy, which researchers hoped would avoid causing significant side effects," Baker explained. "Targeted drugs are designed to knock out specific molecules that occur in abnormal cells, while sparing normal cells. But our work showed that people with the ABCG2 mutation are at increased risk for side effects."

Since diarrhea and skin toxicity limit the use of this drug in some patients, the researchers looked for a specific variation in the ABCG2 gene that could disrupt the function of the ABCG2 protein.

Among patients getting this drug, 44 percent of 124 individuals with the mutation in the ABCG2 gene developed diarrhea after receiving gefitinib; only 12 percent of 108 patients without the mutation developed diarrhea. However, this specific mutation did not cause acne, another side of effect of gefitinib. "Our finding also means that as targeted therapies become common in the years ahead it will be important to have a selection of such drugs so clinicians can choose those that are appropriate to the genetic makeup of the patient," Baker said.

Baker was at The Sidney Kimmel comprehensive Cancer Center at Johns Hopkins when she worked on this project.


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Contact: Bonnie Kourvelas
bonnie.kourvelas@stjude.org
901-495-4815
St. Jude Children's Research Hospital
5-Dec-2006


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