Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449

Charles M. Rudin; Christine L. Hann; John Laterra; Robert L. Yauch; Christopher A. Callahan; Ling Fu; Thomas Holcomb; Jeremy Stinson; Stephen E. Gould; Barbara Coleman; Patricia M. LoRusso; Daniel D. Von Hoff; Frederic J. De Sauvage; Jennifer A. Low

doi:10.1056/NEJMoa0902903

Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449

Charles M. Rudin, Christine L. Hann, John Laterra, Robert L. Yauch, Christopher A. Callahan, Ling Fu, Thomas Holcomb, Jeremy Stinson, Stephen E. Gould, Barbara Coleman, Patricia M. LoRusso, Daniel D. Von Hoff, Frederic J. De Sauvage, Jennifer A. Low

School of Medicine

Research output: Contribution to journal › Article › peer-review

803 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1173-1178
Number of pages	6
Journal	New England Journal of Medicine
Volume	361
Issue number	12
DOIs	https://doi.org/10.1056/NEJMoa0902903
State	Published - Sep 17 2009

ASJC Scopus subject areas

General Medicine

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title = "Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449",

abstract = "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.",

author = "Rudin, {Charles M.} and Hann, {Christine L.} and John Laterra and Yauch, {Robert L.} and Callahan, {Christopher A.} and Ling Fu and Thomas Holcomb and Jeremy Stinson and Gould, {Stephen E.} and Barbara Coleman and LoRusso, {Patricia M.} and {Von Hoff}, {Daniel D.} and {De Sauvage}, {Frederic J.} and Low, {Jennifer A.}",

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AU - Rudin, Charles M.

AU - Hann, Christine L.

AU - Laterra, John

AU - Yauch, Robert L.

AU - Callahan, Christopher A.

AU - Fu, Ling

AU - Holcomb, Thomas

AU - Stinson, Jeremy

AU - Gould, Stephen E.

AU - Coleman, Barbara

AU - LoRusso, Patricia M.

AU - Von Hoff, Daniel D.

AU - De Sauvage, Frederic J.

AU - Low, Jennifer A.

PY - 2009/9/17

Y1 - 2009/9/17

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AB - 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.

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Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449

Abstract

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