Stopping hedgehogs

Antagonists of the Hedgehog pathway inhibit the growth of medulloblastoma tumors.

Jonathan Weitzman(jonathanweitzman@hotmail.com)
Aug 29, 2002

The Hedgehog (Hh) pathway has been associated with embryonic cell fate and the development of neoplasia. Medulloblastomas contain mutations in the transmembrane proteins Patched (Ptch) or Smoothened (Smo) that result in ligand-independent activation of the Hh pathway. In the August 30 Science, Berman and colleagues report the use of cyclopamine, a plant-derived antagonist of the Hh pathway, to block medulloblastoma growth (Science 2002, 297:1559-1561).

Berman et al. studied cells derived from cerebellar tumors from mice with a mutant Ptch allele. Cyclopamine specifically inhibited Hh signaling and medullablastoma proliferation in cell cultures. Cyclopamine treatment also inhibited the expression of cell cycle genes and increased the expression of neuronal markers. Cyclopamine derivatives blocked growth and survival of freshly resected human medulloblastoma cells. Furthermore, Berman et al. showed that cyclopamine could block the growth of medulloblastoma allografts in vivo.

These results open up the possibility of using Hh antagonists...

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