New developments in medulloblastoma treatment: the potential of a cyclopamine-lovastatin combination.
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.
Bar
Eli E
EE
Johns Hopkins University School of Medicine, Department of Pathology, 720 Rutland Avenue, Ross Building 558, Baltimore, MD 21205, USA. ebar1@jhmi.edu
Stearns
Duncan
D
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D002784:Cholesterol / Q000378:metabolism; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008148:Lovastatin / Q000008:administration & dosage; D008527:Medulloblastoma / Q000188:drug therapy* / Q000378:metabolism; D014704:Veratrum Alkaloids / Q000008:administration & dosage
D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014704:Veratrum Alkaloids; D002784:Cholesterol; D008148:Lovastatin; C000541:cyclopamine