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	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Perspective by Friedman, H. S. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article PubMed Citation

ABSTRACT

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. Pretreatment tissue was available for molecular analysis from 26 patients, 7 of whom had had a response and 19 of whom had rapid progression during therapy. No mutations in EGFR or Her2/neu kinase domains were detected in the tumors. Coexpression of EGFRvIII and PTEN was significantly associated with a clinical response (P<0.001; odds ratio, 51; 95 percent confidence interval, 4 to 669). These findings were validated in 33 patients who received similar treatment for glioblastoma at a different institution (P=0.001; odds ratio, 40; 95 percent confidence interval, 3 to 468). In vitro, coexpression of EGFRvIII and PTEN sensitized glioblastoma cells to erlotinib.

Conclusions Coexpression of EGFRvIII and PTEN by glioblastoma cells is associated with responsiveness to EGFR kinase inhibitors.

Source Information

From the Departments of Molecular and Medical Pharmacology and Medicine (I.K.M., C.L.S.), Pathology and Laboratory Medicine (M.Y.W., S.Z., E.Q.D., K.V.L., K.Y., D.J.C., B.L.R., P.N.R., P.S.M.), Human Genetics (J.H.Y.H., S.H.), Biostatistics (S.H.), Neurosurgery (L.M.L.), and Neurology (T.F.C.); the Henry E. Singleton Brain Tumor Program (I.K.M., L.M.L., T.F.C., P.S.M.); the Molecular Biology Institute (I.V., C.L.S.); and the Howard Hughes Medical Institute (C.L.S.) — all at the David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles; the Department of Neurological Surgery, University of California, San Francisco, San Francisco (D.A.H.-K., D.S., M.P.); the Ludwig Institute for Cancer Research at the University of California, San Diego, San Diego (W.K.C.); and the Department of Medical Oncology, Dana–Farber Cancer Institute, the Department of Medicine, Harvard Medical School, and the Broad Institute of Harvard and the Massachusetts Institute of Technology — all in Boston (R.B., T.C.P., J.C.L., W.R.S.).

Drs. Mellinghoff, Wang, and Vivanco contributed equally to the article.

Address reprint requests to Dr. Mischel at the Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave., Center for the Health Sciences, Room 13-321, Los Angeles, CA 90095-1732, or at pmischel{at}mednet.ucla.edu.

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Related Letters:

Response of Glioblastomas to EGFR Kinase Inhibitors
Lassman A. B., Abrey L. E., Gilbert M. R., Mellinghoff I. K., Cloughesy T., Mischel P. S.
Extract | Full Text | PDF  
N Engl J Med 2006; 354:525-526, Feb 2, 2006. Correspondence

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• Yoshimoto, K., Dang, J., Zhu, S., Nathanson, D., Huang, T., Dumont, R., Seligson, D. B., Yong, W. H., Xiong, Z., Rao, N., Winther, H., Chakravarti, A., Bigner, D. D., Mellinghoff, I. K., Horvath, S., Cavenee, W. K., Cloughesy, T. F., Mischel, P. S. (2008). Development of a Real-time RT-PCR Assay for Detecting EGFRvIII in Glioblastoma Samples. Clin. Cancer Res. 14: 488-493 [Abstract] [Full Text]  
• Sathornsumetee, S., Cao, Y., Marcello, J. E., Herndon, J. E. II, McLendon, R. E., Desjardins, A., Friedman, H. S., Dewhirst, M. W., Vredenburgh, J. J., Rich, J. N. (2008). Tumor Angiogenic and Hypoxic Profiles Predict Radiographic Response and Survival in Malignant Astrocytoma Patients Treated With Bevacizumab and Irinotecan. JCO 26: 271-278 [Abstract] [Full Text]  
• Reznik, T. E., Sang, Y., Ma, Y., Abounader, R., Rosen, E. M., Xia, S., Laterra, J. (2008). Transcription-Dependent Epidermal Growth Factor Receptor Activation by Hepatocyte Growth Factor. Mol Cancer Res 6: 139-150 [Abstract] [Full Text]  
• Shirahata, M., Iwao-Koizumi, K., Saito, S., Ueno, N., Oda, M., Hashimoto, N., Takahashi, J. A., Kato, K. (2007). Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis. Clin. Cancer Res. 13: 7341-7356 [Abstract] [Full Text]  
• Beroukhim, R., Getz, G., Nghiemphu, L., Barretina, J., Hsueh, T., Linhart, D., Vivanco, I., Lee, J. C., Huang, J. H., Alexander, S., Du, J., Kau, T., Thomas, R. K., Shah, K., Soto, H., Perner, S., Prensner, J., Debiasi, R. M., Demichelis, F., Hatton, C., Rubin, M. A., Garraway, L. A., Nelson, S. F., Liau, L., Mischel, P. S., Cloughesy, T. F., Meyerson, M., Golub, T. A., Lander, E. S., Mellinghoff, I. K., Sellers, W. R. (2007). Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma. Proc. Natl. Acad. Sci. USA 104: 20007-20012 [Abstract] [Full Text]  
• Hoelzinger, D. B., Demuth, T., Berens, M. E. (2007). Autocrine Factors That Sustain Glioma Invasion and Paracrine Biology in the Brain Microenvironment. JNCI J Natl Cancer Inst 99: 1583-1593 [Abstract] [Full Text]  
• Furnari, F. B., Fenton, T., Bachoo, R. M., Mukasa, A., Stommel, J. M., Stegh, A., Hahn, W. C., Ligon, K. L., Louis, D. N., Brennan, C., Chin, L., DePinho, R. A., Cavenee, W. K. (2007). Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 21: 2683-2710 [Abstract] [Full Text]  
• Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., Chin, L., DePinho, R. A. (2007). Coactivation of Receptor Tyrosine Kinases Affects the Response of Tumor Cells to Targeted Therapies. Science 318: 287-290 [Abstract] [Full Text]  
• Stupp, R., Hegi, M. E., Gilbert, M. R., Chakravarti, A. (2007). Chemoradiotherapy in Malignant Glioma: Standard of Care and Future Directions. JCO 25: 4127-4136 [Abstract] [Full Text]  
• Fan, Q.-W., Cheng, C. K., Nicolaides, T. P., Hackett, C. S., Knight, Z. A., Shokat, K. M., Weiss, W. A. (2007). A Dual Phosphoinositide-3-Kinase {alpha}/mTOR Inhibitor Cooperates with Blockade of Epidermal Growth Factor Receptor in PTEN-Mutant Glioma. Cancer Res. 67: 7960-7965 [Abstract] [Full Text]  
• Kelsen, D. P., Winter, K. A., Gunderson, L. L., Mortimer, J., Estes, N. C., Haller, D. G., Ajani, J. A., Kocha, W., Minsky, B. D., Roth, J. A., Willett, C. G. (2007). Long-Term Results of RTOG Trial 8911 (USA Intergroup 113): A Random Assignment Trial Comparison of Chemotherapy Followed by Surgery Compared With Surgery Alone for Esophageal Cancer. JCO 25: 3719-3725 [Abstract] [Full Text]  
• Ogino, A., Kitao, H., Hirano, S., Uchida, A., Ishiai, M., Kozuki, T., Takigawa, N., Takata, M., Kiura, K., Tanimoto, M. (2007). Emergence of Epidermal Growth Factor Receptor T790M Mutation during Chronic Exposure to Gefitinib in a Non Small Cell Lung Cancer Cell Line. Cancer Res. 67: 7807-7814 [Abstract] [Full Text]  
• Lee, D. H., Lee, G. K., Kong, S.-y., Kook, M. C., Yang, S. K., Park, S. Y., Park, S. H., Keam, B., Park, D. J., Cho, B. Y., Kim, S. W., Chung, K.-W., Lee, E. S., Kim, S. W. (2007). Epidermal growth factor receptor status in anaplastic thyroid carcinoma. J. Clin. Pathol. 60: 881-884 [Abstract] [Full Text]  
• Johnson, B. E., Jackman, D., Janne, P. A. (2007). Rationale for a Phase I Trial of Erlotinib and the Mammalian Target of Rapamycin Inhibitor Everolimus (RAD001) for Patients with Relapsed Non Small Cell Lung Cancer. Clin. Cancer Res. 13: 4628s-4631s [Abstract] [Full Text]  
• Little, S. E., Bax, D. A., Rodriguez-Pinilla, M., Natrajan, R., Messahel, B., Pritchard-Jones, K., Vujanic, G. M., Reis-Filho, J. S., Jones, C. (2007). Multifaceted Dysregulation of the Epidermal Growth Factor Receptor Pathway in Clear Cell Sarcoma of the Kidney. Clin. Cancer Res. 13: 4360-4364 [Abstract] [Full Text]  
• Huang, P. H., Mukasa, A., Bonavia, R., Flynn, R. A., Brewer, Z. E., Cavenee, W. K., Furnari, F. B., White, F. M. (2007). Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma. Proc. Natl. Acad. Sci. USA 104: 12867-12872 [Abstract] [Full Text]  
• Ishiuchi, S., Yoshida, Y., Sugawara, K., Aihara, M., Ohtani, T., Watanabe, T., Saito, N., Tsuzuki, K., Okado, H., Miwa, A., Nakazato, Y., Ozawa, S. (2007). Ca2+-Permeable AMPA Receptors Regulate Growth of Human Glioblastoma via Akt Activation. J. Neurosci. 27: 7987-8001 [Abstract] [Full Text]  
• Wiencke, J. K., Zheng, S., Jelluma, N., Tihan, T., Vandenberg, S., Tamguney, T., Baumber, R., Parsons, R., Lamborn, K. R., Berger, M. S., Wrensch, M. R., Haas-Kogan, D. A., Stokoe, D. (2007). Methylation of the PTEN promoter defines low-grade gliomas and secondary glioblastoma. Neuro Oncol Duke 9: 271-279 [Abstract] [Full Text]  
• Xu, K., Shu, H.-K. G. (2007). EGFR Activation Results in Enhanced Cyclooxygenase-2 Expression through p38 Mitogen-Activated Protein Kinase-Dependent Activation of the Sp1/Sp3 Transcription Factors in Human Gliomas. Cancer Res. 67: 6121-6129 [Abstract] [Full Text]  
• Omuro, A. M.P., Faivre, S., Raymond, E. (2007). Lessons learned in the development of targeted therapy for malignant gliomas. Molecular Cancer Therapeutics 6: 1909-1919 [Abstract] [Full Text]  
• French, P. J., Peeters, J., Horsman, S., Duijm, E., Siccama, I., van den Bent, M. J., Luider, T. M., Kros, J. M., van der Spek, P., Sillevis Smitt, P. A. (2007). Identification of Differentially Regulated Splice Variants and Novel Exons in Glial Brain Tumors Using Exon Expression Arrays. Cancer Res. 67: 5635-5642 [Abstract] [Full Text]  
• Yamasaki, F., Johansen, M. J., Zhang, D., Krishnamurthy, S., Felix, E., Bartholomeusz, C., Aguilar, R. J., Kurisu, K., Mills, G. B., Hortobagyi, G. N., Ueno, N. T. (2007). Acquired Resistance to Erlotinib in A-431 Epidermoid Cancer Cells Requires Down-regulation of MMAC1/PTEN and Up-regulation of Phosphorylated Akt. Cancer Res. 67: 5779-5788 [Abstract] [Full Text]  
• Pelloski, C. E., Ballman, K. V., Furth, A. F., Zhang, L., Lin, E., Sulman, E. P., Bhat, K., McDonald, J. M., Yung, W.K. A., Colman, H., Woo, S. Y., Heimberger, A. B., Suki, D., Prados, M. D., Chang, S. M., Barker, F. G. II, Buckner, J. C., James, C. D., Aldape, K. (2007). Epidermal Growth Factor Receptor Variant III Status Defines Clinically Distinct Subtypes of Glioblastoma. JCO 25: 2288-2294 [Abstract] [Full Text]  
• Rittie, L., Kansra, S., Stoll, S. W., Li, Y., Gudjonsson, J. E., Shao, Y., Michael, L. E., Fisher, G. J., Johnson, T. M., Elder, J. T. (2007). Differential ErbB1 Signaling in Squamous Cell versus Basal Cell Carcinoma of the Skin. Am. J. Pathol. 170: 2089-2099 [Abstract] [Full Text]  
• Ohgaki, H., Kleihues, P. (2007). Genetic Pathways to Primary and Secondary Glioblastoma. Am. J. Pathol. 170: 1445-1453 [Abstract] [Full Text]  
• Bradley, S. V., Holland, E. C., Liu, G. Y., Thomas, D., Hyun, T. S., Ross, T. S. (2007). Huntingtin Interacting Protein 1 Is a Novel Brain Tumor Marker that Associates with Epidermal Growth Factor Receptor. Cancer Res. 67: 3609-3615 [Abstract] [Full Text]  
• Johns, T. G., Perera, R. M., Vernes, S. C., Vitali, A. A., Cao, D. X., Cavenee, W. K., Scott, A. M., Furnari, F. B. (2007). The Efficacy of Epidermal Growth Factor Receptor-Specific Antibodies against Glioma Xenografts Is Influenced by Receptor Levels, Activation Status, and Heterodimerization. Clin. Cancer Res. 13: 1911-1925 [Abstract] [Full Text]  
• Cruz, J., Ocana, A, Del Barco, E, Pandiella, A (2007). Targeting receptor tyrosine kinases and their signal transduction routes in head and neck cancer. Ann Oncol 18: 421-430 [Abstract] [Full Text]  
• Sarkaria, J. N., Yang, L., Grogan, P. T., Kitange, G. J., Carlson, B. L., Schroeder, M. A., Galanis, E., Giannini, C., Wu, W., Dinca, E. B., James, C. D. (2007). Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Molecular Cancer Therapeutics 6: 1167-1174 [Abstract] [Full Text]  
• Rubio-Viqueira, B., Mezzadra, H., Nielsen, M. E., Jimeno, A., Zhang, X., Iacobuzio-Donahue, C., Maitra, A., Hidalgo, M., Altiok, S. (2007). Optimizing the development of targeted agents in pancreatic cancer: tumor fine-needle aspiration biopsy as a platform for novel prospective ex vivo drug sensitivity assays. Molecular Cancer Therapeutics 6: 515-523 [Abstract] [Full Text]  
• Failly, M., Korur, S., Egler, V., Boulay, J.-L., Lino, M. M., Imber, R., Merlo, A. (2007). Combination of sublethal concentrations of epidermal growth factor receptor inhibitor and microtubule stabilizer induces apoptosis of glioblastoma cells. Molecular Cancer Therapeutics 6: 773-781 [Abstract] [Full Text]  
• Solit, D. B., Rosen, N. (2007). Targeting HER2 in Prostate Cancer: Where to Next?. JCO 25: 241-243 [Full Text]  
• Mellinghoff, I. K., Cloughesy, T. F., Mischel, P. S. (2007). PTEN-Mediated Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors. Clin. Cancer Res. 13: 378-381 [Abstract] [Full Text]  
• Shrader, M., Pino, M. S., Brown, G., Black, P., Adam, L., Bar-Eli, M., Dinney, C. P.N., McConkey, D. J. (2007). Molecular correlates of gefitinib responsiveness in human bladder cancer cells. Molecular Cancer Therapeutics 6: 277-285 [Abstract] [Full Text]