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Published at www.nejm.org September 2, 2009 (10.1056/NEJMoa0902903)

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SUMMARY

Medulloblastoma is the most common malignant brain tumor in children. Aberrant activation of the hedgehog signaling pathway is strongly implicated in the development of some cases of medulloblastoma. A 26-year-old man with metastatic medulloblastoma that was refractory to multiple therapies was treated with a novel hedgehog pathway inhibitor, GDC-0449; treatment resulted in rapid (although transient) regression of the tumor and reduction of symptoms. Molecular analyses of tumor specimens obtained before treatment suggested that there was activation of the hedgehog pathway, with loss of heterozygosity and somatic mutation of the gene encoding patched homologue 1 (PTCH1), a key negative regulator of hedgehog signaling.

Source Information

From the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore (C.M.R., C.L.H., J.L., B.C.); Genentech, South San Francisco, CA (R.L.Y., C.A.C., L.F., T.H., J.S., S.E.G., F.J.S., J.A.L.); Karmanos Cancer Institute, Wayne State University, Detroit (P.M.L.); and Translational Genomics (TGen), Scottsdale Clinical Research Institute, Scottsdale, AZ (D.D.V.H.).

This article (10.1056/NEJMoa0902903) was published on September 2, 2009, at NEJM.org.

Address reprint requests to Dr. Rudin at Johns Hopkins University, David H. Koch Cancer Research Bldg., Rm. 544, 1550 Orleans St., Baltimore, MD 21231, or at rudin{at}jhmi.edu.

Full Text of this Article

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