作者
Ingo K Mellinghoff, Maria Y Wang, Igor Vivanco, Daphne A Haas-Kogan, Shaojun Zhu, Ederlyn Q Dia, Kan V Lu, Koji Yoshimoto, Julie HY Huang, Dennis J Chute, Bridget L Riggs, Steve Horvath, Linda M Liau, Webster K Cavenee, P Nagesh Rao, Rameen Beroukhim, Timothy C Peck, Jeffrey C Lee, William R Sellers, David Stokoe, Michael Prados, Timothy F Cloughesy, Charles L Sawyers, Paul S Mischel
发表日期
2005/11/10
期刊
New England Journal of Medicine
卷号
353
期号
19
页码范围
2012-2024
出版商
Massachusetts Medical Society
简介
Background
The epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients have a response to EGFR kinase inhibitors. The mechanism of responsiveness of glioblastomas to these inhibitors is unknown.
Methods
We sequenced kinase domains in the EGFR and human EGFR type 2 (Her2/neu) genes and analyzed the expression of EGFR, EGFR deletion mutant variant III (EGFRvIII), and the tumor-suppressor protein PTEN in recurrent malignant gliomas from patients who had received EGFR kinase inhibitors. We determined the molecular correlates of clinical response, validated them in an independent data set, and identified effects of the molecular abnormalities in vitro.
Results
Of 49 patients with recurrent malignant glioma who were treated with EGFR kinase inhibitors, 9 had tumor shrinkage of at least 25 percent …
引用总数
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IK Mellinghoff, MY Wang, I Vivanco, DA Haas-Kogan… - New England Journal of Medicine, 2005