(MEMPHIS, Tenn. March 27, 2014) The quest to improve survival of children with a high-risk brain tumor has led St. Jude Children's Research Hospital investigators to two drugs already used to treat adults with breast, pancreatic, lung and other cancers. The study was published today online ahead of print in the journal Cancer Cell.
Researchers demonstrated that the drugs pemetrexed and gemcitabine killed cells from mouse and human brain tumors, called group 3 medulloblastoma, growing in the laboratory. Medulloblastoma is diagnosed in about 400 children annually in the U.S., making it the most common pediatric brain tumor. Of the four distinct medulloblastoma subtypes, patients with group 3 medulloblastoma have the worst prognosis.
Used together, pemetrexed and gemcitabine doubled life expectancy of mice with human group 3 medulloblastoma, compared to untreated mice. When pemetrexed and gemcitabine were combined with two chemotherapy drugs currently used to treat pediatric medulloblastoma, the mice lived even longer.
The drugs were identified by screening the St. Jude library of 7,389 compounds looking for ones that targeted group 3 mouse tumor cells rather than normal mouse brain cells. The library included all 830 drugs U.S. Food and Drug Administration (FDA) approval. Pemetrexed and gemcitabine emerged as the top candidates, based in part on their ability to kill group 3 medulloblastoma tumor cells at concentrations that researchers showed were safe and achievable in patients.
"Our focus was to identify drugs that we could move quickly from the laboratory to the clinic where new chemotherapy options are desperately needed for these high-risk medulloblastoma patients," said the study's corresponding author Martine Roussel, Ph.D., a member of the St. Jude Department of Tumor Cell Biology. "As a basic scientist, it is exciting to be able to translate a laboratory discovery into drugs that are now being used in a cli
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St. Jude Children's Research Hospital