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Bar EE, Stearns D.
New developments in medulloblastoma treatment: the
potential of a cyclopamine - lovastatin combination.
Expert Opin Investig Drugs. 2008 Feb;17(2):185-95
Johns Hopkins University School of Medicine,
Department of Pathology, 720 Rutland Avenue, Ross Building 558,
Baltimore, MD 21205, USA.
ebar1@jhmi.edu
Pediatric brain tumors are the most common cause of
cancer-related death in children. Despite advances in
neuroimaging, surgical techniques, radiotherapy and the
introduction of new chemotherapeutic agents, up to 30% of all
patients diagnosed with medulloblastoma will die from their
disease, thus underscoring the need for more effective
treatments. This review explores the relationship between
cholesterol and cancer in light of a recent study that
demonstrated that the hedgehog (Hh) antagonist cyclopamine
blocked expression of the Hh pathway targets PTCH1 and GLI1,
lowered Bcl2 levels and increased apoptosis in medulloblastoma
cells. In addition, Hh pathway blockade sensitized
medulloblastoma to the effects of the proapoptotic,
cholesterol-lowering agent lovastatin. The use of Hh pathway
antagonists and cholesterol synthesis inhibitors in
medulloblastoma is a novel and exciting approach as it targets
pathways crucial for tumor survival. The safety of such
approach, however, still needs to be tested in animal models of
the disease before its application in human patients.
PMID: 18230052
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