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Targeted therapy knocks out pediatric brain cancer in mice


Scientists have identified what may be the first nontoxic treatment for a subset of medulloblastoma, the most common type of malignant pediatric brain tumor. The finding is encouraging in that such precise, targeted therapies may someday replace traditional treatments that can have overwhelmingly negative side effects for pediatric cancer patients. The research is published in the September issue of Cancer Cell.

"Therapy for pediatric cancers of the central nervous system has not improved significantly in the last three decades," explains study author Dr. Tom Curran from St. Jude Children’s Research Hospital in Memphis, Tennessee. "This is partly due to the absence of adequate model systems for testing novel therapies." Dr. Curran and colleagues used a mouse model of medulloblastoma that they had developed to examine whether selective inhibition of the Sonic Hedgehog (Shh) signaling pathway could interfere with the development and progression of the disease. Previous studies have implicated the Shh pathway in human medulloblastoma formation.

Treatment of the mice with a small molecule inhibitor of Shh, HhAntag, resulted in elimination of medulloblastoma. HhAntag administration was associated with the suppression of multiple genes expressed in medulloblastoma as well as reduced cell proliferation and an increase in tumor cell death. Importantly, high doses of HhAntag completely eradicated the tumors, and long-term treatment prolonged medulloblastoma-free survival. No toxic side effects of HhAntag treatment were observed in the mice.

The researchers conclude that the development of compounds that selectively block Shh may be an appropriate direction for designing effective, nontoxic treatments for medulloblastoma. "Ultimately, it is likely that success in treating cancer will require the use of several compounds in concert that target distinct pathways important for tumor cell growth. Our mouse studies with HhAntag offer the hope that such precise, targeted molecular interventions could spare children from the devastating effects of surgery, toxic chemotherapy, and exposure to high doses of radiation," offers Dr. Curran.

Heidi Hardman | EurekAlert!
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