Medulloblastoma growth inhibition by Hedgehog pathway blockade

David M. Berman, Sunil S. Karhadkar, Andrew R. Hallahan, Joel I. Pritchard, Charles G. Eberhart, D. Neil Watkins, James K. Chen, Michael K. Cooper, Jussi Taipale, James M. Olson, Philip A. Beachy

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1559-1561
Number of pages3
JournalScience
Volume297
Issue number5586
DOIs
StatePublished - Aug 30 2002
Externally publishedYes

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    Berman, D. M., Karhadkar, S. S., Hallahan, A. R., Pritchard, J. I., Eberhart, C. G., Watkins, D. N., Chen, J. K., Cooper, M. K., Taipale, J., Olson, J. M., & Beachy, P. A. (2002). Medulloblastoma growth inhibition by Hedgehog pathway blockade. Science, 297(5586), 1559-1561. https://doi.org/10.1126/science.1073733