Aug 25, 2014 01:20 PM EDT
Anti-depressant medication may be able to combat one of the most common brain cancers in children, according to a recent study.
Researchers at the Cancer and Blood Diseases Institute (CBDI) at Cincinnati Children's Hospital Medical Center have identified a novel molecular pathway that causes an aggressive form of medulloblastoma, a highly malignant primary brain tumor.
"Although current treatments improve survival rates, patients suffer severe side effects and relapse tumors carry mutations that resist treatment," Q. Richard Lu, lead investigator of the study and a scientific director of the Brain Tumor Center, part of the CBDI at Cincinnati Children's. "This underscores an urgent need for alternative targeted therapies, and we have identified a potent tumor suppressor that could help a subset of patients with an aggressive form of medulloblastoma."
Using genetically-engineered mice to model human medulloblastoma, the research team identified a gene called GNAS that encodes a protein called Gsa. Gsa kicks off a signaling cascade that researchers found suppresses the initiation of an aggressive form of medulloblastoma driven by a protein called Sonic hedgehog -- considered one of the most important molecules in tissue formation and development.
Researchers used an anti-depressant medication called Rolipram -- approved for behavioral therapy for use in Europe and Japan -- to treat mice that were engineered not to express the GNAS gene. Lack of GNAS allowed aggressive formation of medulloblastoma tumors in neural progenitor cells of the GNAS mutant mice.
The medicine elevated levels of a molecule called cAMP, which restored the GNAS-Gsa pathway's tumor suppression function. This caused the tumors to shrink and subside. The study also suggests that elevating cAMP levels in cells enhances the potency of Sonic hedgehog inhibitors, currently being tested in clinical trials to fight tumor growth.
The results suggest repurposing the anti-depressant medication to target the new pathway may help combat one of the most common brain cancers in children.
The findings were recently published in Nature Medicine.
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