Drugs that block the enzyme Odc prevent the onset of cancers that would otherwise be triggered by a family of cancer-causing genes called Myc, according to investigators at St. Jude Children's Research Hospital. The researchers showed that disabling Odc disrupts the ability of Myc genes to speed up cell division. Myc controls the expression of many genes; but the investigators showed that disrupting just this one target delays the onset of cancer in a laboratory model that mimics human Burkitt lymphoma (BL). BL is a cancer of B lymphocytes, immune system cells that produce antibodies.

The researchers showed that either treatment with Odc-suppressing drug DFMO or the loss of one of the two copies of the Odc gene in a B lymphocyte impairs Myc's ability to stimulate uncontrolled cell division. The team made these findings in E-Myc laboratory models, which overexpress Myc in B cells and are widely used in laboratory studies of cancer.

The discovery of the link between Odc and Myc in tumor development is significant because Myc genes are activated in up to 70 percent of human cancers. Therefore, a drug that disrupts their activity by disabling Odc might prevent or slow the development of a wide variety of cancers, including breast, colon, lung and prostate cancers. However, while DFMO treatment was effective in preventing lymphoma development in the E-Myc model, it only worked when cells had an intact tumor-suppressing mechanism called the Arf-p53 pathway. This suggests that cancers carrying mutations that disable Arf-p53 would not respond to DFMO, the researchers said.

"Each time a cell divides it must make a copy of the genome to transmit it to the new daughter cells, a process that is vulnerable to mistakes that cause mutations," said John Cleveland, Ph.D., a member of the Department of Biochemistry at St. Jude. "Curtailing cell division reduces the chance that cancer-causing mutations will occur, which is especially important in cells that already
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Contact: Kelly Perry
kelly.perry@stjude.org
901-495-3306
St. Jude Children's Research Hospital
16-May-2005

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