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Brain tumor study reveals why treatment efforts fail in genetic disorder

St. Louis, Jan. 1, 2004 -- Drugs used to treat the tumors common in people with a disorder called neurofibromatosis 1 rarely work, and scientists now know why. The chemotherapy drugs target a group of related proteins, call RAS proteins, which are thought to be responsible for these tumors. But researchers at Washington University School of Medicine in St. Louis found that the disease affects only one member of the protein family, and it happens to be the one form of RAS that does not respond well to these particular treatments.

The study, which will appear in the Jan. 1 issue of the journal Cancer Research, suggests where researchers should now look for more promising approaches to treating neurofibromatosis tumors, and may help scientists understand other cancers related to RAS.

"The downside is our study proves we're not using the right therapies for this particular problem," says principal investigator David H. Gutmann, M.D., Ph.D., the Donald O. Schnuck Family Professor of Neurology and professor of genetics and of pediatrics. "But there's a chance to make lemonade out of this lemon: We now have a rational reason for why these drugs aren't working, so we should be able to explore new, more effective treatment options."

About one in 4,000 newborns has neurofibromatosis 1, in which every cell in the body has one normal and one mutated copy of a gene called NF1. If a cell's normal copy also is mutated, tumors can form. Children with neurofibromatosis 1 are therefore predisposed to developing a variety of serious complications as they grow older, including skin, spine and brain cancers.

Scientists previously found that RAS proteins become overly active when both copies of the NF1 gene are abnormal in tumors from patients with neurofibromatosis 1. So physicians have tried treating these tumors with drugs that prevent RAS activity. Unfortunately, the results have been disappointing.

To understand why, Gutmann's team examined
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Contact: Gila Z. Reckess
reckessg@wustl.edu
314-286-0109
Washington University School of Medicine
1-Jan-2005


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