Cyclopamine Blocks Tumors by Inhibiting Hedgehog Pathway

A recent study revealed that activation of the Hedgehog signaling pathway caused a significant subset of small-cell lung cancers in mice and that cyclopamine, a naturally occurring inhibitor of the Hedgehog pathway, could block growth of these tumors. The study appeared March 5, 2003, in the online edition of Nature.

The Hedgehog pathway becomes activated when the function of one of the pathway's key genes, called Patched, is lost through mutation. The protein produced by Patched normally represses a downstream member of the Hedgehog pathway--a protein called Smoothened. Loss of Patched activates the Smoothened protein, turning on the Hedgehog pathway and leading to malignancy. Cyclopamine, a compound isolated from a plant extract, blocked the Hedgehog pathway in mouse embryos by inhibiting the activity of Smoothened.

Earlier work had implicated the Hedgehog pathway in the development of several types of cancers, including basal cell carcinoma and medulloblastoma. The current study was conducted by investigators from Johns Hopkins University (Baltimore, MD, USA) and Curis, Inc. (Cambridge, MA, USA). A patent application describing the use of cyclopamine to selectively block the Hedgehog pathway for therapeutic purposes has been filed by Johns Hopkins and licensed to Curis.




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Johns Hopkins University
Curis Inc.