Nature's hedgehog blocker

Curis Inc., which has focused on commercializing therapeutics based on the Hedgehog signaling pathway, hopes to benefit from a serendipitous finding in the field. In last week's Nature, CRIS collaborators at Johns Hopkins University School of Medicine (Baltimore, Md.) and colleagues published that cyclopamine, a plant-derived teratogen that inhibits the Hedgehog pathway, could be useful to treat basal cell carcinoma and other tumors associated with altered Hedgehog signaling.

Hedgehog, a secreted protein, signals by binding to a complex between the transmembrane receptors Patched and Smoothened. When Hedgehog is bound, suppression of Smoothened activity is relieved and downstream signaling proteins activate expression of various target genes in the nucleus. Mutations in Patched that activate the Hedgehog pathway in the absence of Hedgehog can cause abnormal cell growth, and have been associated with basal cell carcinoma...