Drug Developer Interested in Hedgehog Pathway Suppressor

Researchers have found that a mutation resulting in the deletion of a gene that codes for a protein that suppresses the Hedgehog signaling pathway is characteristic of human childhood medulloblastoma.

A group of Italian investigators reported in the July 12, 2004, online edition of the Proceedings of the [U.S.] National Academy of Sciences that reduction of expression or deletion of the chromosome 17 gene RENKCTD11 typifies most cases of medulloblastoma. RENKCTD11 inhibits medulloblastoma cell proliferation and colony formation in vitro and suppresses xenograft tumor growth in vivo. RENKCTD11 seems to inhibit medulloblastoma growth by suppressing the Hedgehog pathway because it antagonizes the Gli-mediated transactivation of Hedgehog target genes by affecting Gli1 nuclear transfer, and its growth inhibitory activity is impaired by Gli1 inactivation.

These findings are of particular interest to the drug development company Curis, Inc. (Cambridge, MA, USA), which has developed several cancer drug candidates designed to block or antagonize abnormal activation of the Hedgehog pathway. Dr. Lee Rubin, CSO of Curis, said, "This study provides strong corroborative evidence that the mechanism by which certain cancers promote their tumor growth is by exploiting some means of up-regulating the Hedgehog signaling pathway, in this instance by removal of a normal Hedgehog pathway suppressor. We believe that Hedgehog pathway inhibition technologies will constitute an important and promising approach to the potential treatment of medulloblastoma and other cancers.”



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