Brief Report: Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449.

被引：805

作者：

Rudin, Charles M. ^{[1
]}

Hann, Christine L. ^{[1
]}

Laterra, John ^{[1
]}

Yauch, Robert L. ^{[2
]}

Callahan, Christopher A. ^{[2
]}

Fu, Ling ^{[2
]}

Holcomb, Thomas ^{[2
]}

Stinson, Jeremy ^{[2
]}

Gould, Stephen E. ^{[2
]}

Coleman, Barbara ^{[1
]}

LoRusso, Patricia M. ^{[3
]}

Von Hoff, Daniel D. ^{[4
]}

de Sauvage, Frederic J. ^{[2
]}

Low, Jennifer A. ^{[2
]}

机构：

[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA

[2] Genentech Inc, San Francisco, CA 94080 USA

[3] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA

[4] Scottsdale Clin Res Inst, Scottsdale, AZ USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2009年 / 361卷 / 12期

关键词：

CHRONIC MYELOID-LEUKEMIA; CELL LUNG-CANCER; SONIC HEDGEHOG; TUMOR; RESISTANCE; MUTATIONS; IMATINIB; GEFITINIB; STAGE; MICE;

D O I：

10.1056/NEJMoa0902903

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1173 / 1178

页数：6

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