Medulloblastoma growth inhibition by hedgehog pathway blockade.

Berman DM, Karhadkar SS, Hallahan AR, Pritchard JI, Eberhart CG, Watkins DN, Chen JK, Cooper MK, Taipale J, Olson JM, Beachy PA
Science. 2002 297 (5586): 1559-61

PMID: 12202832 · DOI:10.1126/science.1073733

Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. This compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, thus establishing a specific role for Hh pathway activity in medulloblastoma growth.

MeSH Terms (18)

Animals Antineoplastic Agents Bicuculline Cell Differentiation Cell Division Cerebellar Neoplasms Disease Models, Animal Hedgehog Proteins Humans Medulloblastoma Membrane Proteins Mice Mice, Nude Patched Receptors Receptors, Cell Surface Signal Transduction Trans-Activators Tumor Cells, Cultured

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