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New strategy likely to speed drug development for rare cancers
Date:9/15/2011

her cancers where treatment options are limited and the outlook remains bleak. While overall childhood cancer survival rates are now almost 80 percent, ependymoma remains incurable in up to 40 percent of patients. The tumor is found in 150 to 200 U.S. children annually, making it the third most common pediatric brain tumor. Treatment has changed little in the past 40 years and is limited to surgery and radiation.

Along with identifying and prioritizing drug development candidates against ependymoma, the research provided insight into the tumor's biology. The screening identified several messenger proteins, known as kinases, as possible new regulators of the tumor cell proliferation that makes cancer deadly. The abnormal tumor kinase activity occurred in certain pathways in tumor cells, including the insulin-signaling pathway and the centrosome cycle.

This study builds on earlier research led by Gilbertson that showed ependymoma includes nine different tumor subtypes. Each begins when particular mutations occur in stem cells from different regions of the brain or spine. Stem cells are the specialized cells that can divide and take on more specific functions.

For this project, investigators focused on a subtype D ependymoma. In earlier research, Gilbertson and his colleagues showed that extra copies of the EPHB2 gene caused this tumor subtype. The investigators used this information to develop an accurate model of subtype D ependymomas in mice. The mouse model includes the same mutation in the same neural stem cell responsible for the human disease and was crucial for speeding drug development.

Researchers used an automated system to check 5,303 existing drugs, natural products and other compounds for activity against four different types of mouse brain cells, including normal neural stem cells, subtype D ependymoma tumor cells and cells from a different brain tumor.

Of the 634 compounds that showed activity against subtype
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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

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