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Technique could speed new medulloblastoma drugs

emical signaling pathway triggers and sustains the cancer by identifying key genes that are linked to that pathway. The investigators proved that this strategy is valid by demonstrating that it is possible to assign children with medulloblastoma into specific groups, depending on which biochemical signaling pathway is abnormally active. Based on this classification, novel drugs designed to block a key protein in each specific pathway could be correctly administered to the children most likely to respond to them.

"Our strategy would ensure that a new drug would get a fair trial by using it to treat only the appropriate children," Gilbertson said. "That will be important as novel drugs are developed to treat medulloblastoma." St. Jude researchers reported in the September 2004 issue of Cancer Cell that a novel drug called ShhAntag effectively targets such a pathway in mice with medulloblastoma and dramatically reduces the size of the tumor: http://www.stjude.org/media/0,2561,453_5297_12301,00.html.

The St. Jude strategy overcomes two problems that often pose barriers to molecular targeted therapies. First, not all children have the same gene mutations that cause a specific cancer, Gilbertson said, so a novel therapy that targets only a gene known to cause the cancer in one group of children will not be effective in a child whose same cancer is caused by a different mutation. Secondly, scientists have identified only a few genes that are potential targets for novel drugs in medulloblastomas, and even fewer in other brain tumors. The current solution to that problem--to identify the DNA sequence of all the genes in each child's tumor to determine which ones are mutated--is an enormous and expensive undertaking, he said.

However, the St. Jude team used an approach for identifying the signaling pathways that cause medulloblastoma in different groups of children.

"Our strategy is somewhat analogous to the link between a home's electric
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Contact: Bonnie Kourvelas
media@stjude.org
901-495-3306
St. Jude Children's Research Hospital
17-Apr-2006


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