Report

Medulloblastoma Growth Inhibition by Hedgehog Pathway Blockade

Science  30 Aug 2002:
Vol. 297, Issue 5586, pp. 1559-1561
DOI: 10.1126/science.1073733

You are currently viewing the abstract.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.

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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: jolson{at}fhcrc.org (J.M.O.) and pbeachy{at}jhmi.edu (P.A.B.)

View Full Text

Cited By...