FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 353:2012-2024 November 10, 2005 Number 19 Next

	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.

Full Text of this Article

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

This article has been cited by other articles:

• Chang, S. M., Lamborn, K. R., Kuhn, J. G., Yung, W.K. A., Gilbert, M. R., Wen, P. Y., Fine, H. A., Mehta, M. P., DeAngelis, L. M., Lieberman, F. S., Cloughesy, T. F., Robins, H. I., Abrey, L. E., Prados, M. D., North American Brain Tumor Consortium, (2008). Neurooncology clinical trial design for targeted therapies: Lessons learned from the North American Brain Tumor Consortium. Neuro Oncol 10: 631-642 [Abstract] [Full Text]  
• Hamstra, D. A., Galban, C. J., Meyer, C. R., Johnson, T. D., Sundgren, P. C., Tsien, C., Lawrence, T. S., Junck, L., Ross, D. J., Rehemtulla, A., Ross, B. D., Chenevert, T. L. (2008). Functional Diffusion Map As an Early Imaging Biomarker for High-Grade Glioma: Correlation With Conventional Radiologic Response and Overall Survival. JCO 26: 3387-3394 [Abstract] [Full Text]  
• Colman, H., Aldape, K. (2008). Molecular Predictors in Glioblastoma: Toward Personalized Therapy. Arch Neurol 65: 877-883 [Abstract] [Full Text]  
• Maira, S.-M., Stauffer, F., Brueggen, J., Furet, P., Schnell, C., Fritsch, C., Brachmann, S., Chene, P., De Pover, A., Schoemaker, K., Fabbro, D., Gabriel, D., Simonen, M., Murphy, L., Finan, P., Sellers, W., Garcia-Echeverria, C. (2008). Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Molecular Cancer Therapeutics 7: 1851-1863 [Abstract] [Full Text]  
• Williams, R. (2008). Paul Mischel: All about brains. J. Cell Biol. 181: 1044-1045 [Full Text]  
• Kondo, E., Tanaka, T., Miyake, T., Ichikawa, T., Hirai, M., Adachi, M., Yoshikawa, K., Ichimura, K., Ohara, N., Moriwaki, A., Date, I., Ueda, R., Yoshino, T. (2008). Potent synergy of dual antitumor peptides for growth suppression of human glioblastoma cell lines. Molecular Cancer Therapeutics 7: 1461-1471 [Abstract] [Full Text]  
• Thorarinsdottir, H. K., Santi, M., McCarter, R., Rushing, E. J., Cornelison, R., Jales, A., MacDonald, T. J. (2008). Protein Expression of Platelet-Derived Growth Factor Receptor Correlates with Malignant Histology and PTEN with Survival in Childhood Gliomas. Clin. Cancer Res. 14: 3386-3394 [Abstract] [Full Text]  
• Purow, B. W., Sundaresan, T. K., Burdick, M. J., Kefas, B. A., Comeau, L. D., Hawkinson, M. P., Su, Q., Kotliarov, Y., Lee, J., Zhang, W., Fine, H. A. (2008). Notch-1 regulates transcription of the epidermal growth factor receptor through p53. Carcinogenesis 29: 918-925 [Abstract] [Full Text]  
• Soeda, A., Inagaki, A., Oka, N., Ikegame, Y., Aoki, H., Yoshimura, S.-i., Nakashima, S., Kunisada, T., Iwama, T. (2008). Epidermal Growth Factor Plays a Crucial Role in Mitogenic Regulation of Human Brain Tumor Stem Cells. J. Biol. Chem. 283: 10958-10966 [Abstract] [Full Text]  
• Baselga, J., Rosen, N. (2008). Determinants of RASistance to Anti-Epidermal Growth Factor Receptor Agents. JCO 26: 1582-1584 [Full Text]  
• Lee, H., Kong, S. W., Park, P. J. (2008). Integrative analysis reveals the direct and indirect interactions between DNA copy number aberrations and gene expression changes. Bioinformatics 24: 889-896 [Abstract] [Full Text]  
• Diehn, M., Nardini, C., Wang, D. S., McGovern, S., Jayaraman, M., Liang, Y., Aldape, K., Cha, S., Kuo, M. D. (2008). From the Cover: Identification of noninvasive imaging surrogates for brain tumor gene-expression modules. Proc. Natl. Acad. Sci. USA 105: 5213-5218 [Abstract] [Full Text]  
• Gilg, A. G., Tye, S. L., Tolliver, L. B., Wheeler, W. G., Visconti, R. P., Duncan, J. D., Kostova, F. V., Bolds, L. N., Toole, B. P., Maria, B. L. (2008). Targeting Hyaluronan Interactions in Malignant Gliomas and Their Drug-Resistant Multipotent Progenitors. Clin. Cancer Res. 14: 1804-1813 [Abstract] [Full Text]  
• Brandes, A. A., Franceschi, E., Tosoni, A., Hegi, M. E., Stupp, R. (2008). Epidermal Growth Factor Receptor Inhibitors in Neuro-oncology: Hopes and Disappointments. Clin. Cancer Res. 14: 957-960 [Abstract] [Full Text]  
• Ocana, A., Pandiella, A. (2008). Identifying Breast Cancer Druggable Oncogenic Alterations: Lessons Learned and Future Targeted Options. Clin. Cancer Res. 14: 961-970 [Abstract] [Full Text]  
• de la Iglesia, N., Konopka, G., Puram, S. V., Chan, J. A., Bachoo, R. M., You, M. J., Levy, D. E., DePinho, R. A., Bonni, A. (2008). Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway. Genes Dev. 22: 449-462 [Abstract] [Full Text]  
• Wang, S., Guo, P., Wang, X., Zhou, Q., Gallo, J. M. (2008). Preclinical pharmacokinetic/pharmacodynamic models of gefitinib and the design of equivalent dosing regimens in EGFR wild-type and mutant tumor models. Molecular Cancer Therapeutics 7: 407-417 [Abstract] [Full Text]  
• Ziegler, D. S., Kung, A. L., Kieran, M. W. (2008). Anti-Apoptosis Mechanisms in Malignant Gliomas. JCO 26: 493-500 [Abstract] [Full Text]  
• Sawai, A., Chandarlapaty, S., Greulich, H., Gonen, M., Ye, Q., Arteaga, C. L., Sellers, W., Rosen, N., Solit, D. B. (2008). Inhibition of Hsp90 Down-regulates Mutant Epidermal Growth Factor Receptor (EGFR) Expression and Sensitizes EGFR Mutant Tumors to Paclitaxel. Cancer Res. 68: 589-596 [Abstract] [Full Text]  
• Guo, A., Villen, J., Kornhauser, J., Lee, K. A., Stokes, M. P., Rikova, K., Possemato, A., Nardone, J., Innocenti, G., Wetzel, R., Wang, Y., MacNeill, J., Mitchell, J., Gygi, S. P., Rush, J., Polakiewicz, R. D., Comb, M. J. (2008). Signaling networks assembled by oncogenic EGFR and c-Met. Proc. Natl. Acad. Sci. USA 105: 692-697 [Abstract] [Full Text]  
• 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 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]  
• Riely, G. J., Politi, K. A., Miller, V. A., Pao, W. (2006). Update on Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer. Clin. Cancer Res. 12: 7232-7241 [Abstract] [Full Text]  
• Nicholas, M. K., Lukas, R. V., Jafri, N. F., Faoro, L., Salgia, R. (2006). Epidermal Growth Factor Receptor-Mediated Signal Transduction in the Development and Therapy of Gliomas. Clin. Cancer Res. 12: 7261-7270 [Abstract] [Full Text]  
• Wong, K.-K., Tsang, Y. T.M., Chang, Y.-M., Su, J., Di Francesco, A. M., Meco, D., Riccardi, R., Perlaky, L., Dauser, R. C., Adesina, A., Bhattacharjee, M., Chintagumpala, M., Lau, C. C. (2006). Genome-Wide Allelic Imbalance Analysis of Pediatric Gliomas by Single Nucleotide Polymorphic Allele Array. Cancer Res. 66: 11172-11178 [Abstract] [Full Text]  
• Maher, E. A., Brennan, C., Wen, P. Y., Durso, L., Ligon, K. L., Richardson, A., Khatry, D., Feng, B., Sinha, R., Louis, D. N., Quackenbush, J., Black, P. McL., Chin, L., DePinho, R. A. (2006). Marked Genomic Differences Characterize Primary and Secondary Glioblastoma Subtypes and Identify Two Distinct Molecular and Clinical Secondary Glioblastoma Entities. Cancer Res. 66: 11502-11513 [Abstract] [Full Text]  
• Horvath, S., Zhang, B., Carlson, M., Lu, K. V., Zhu, S., Felciano, R. M., Laurance, M. F., Zhao, W., Qi, S., Chen, Z., Lee, Y., Scheck, A. C., Liau, L. M., Wu, H., Geschwind, D. H., Febbo, P. G., Kornblum, H. I., Cloughesy, T. F., Nelson, S. F., Mischel, P. S. (2006). Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target. Proc. Natl. Acad. Sci. USA 103: 17402-17407 [Abstract] [Full Text]  
• Krueger, K. E., Srivastava, S. (2006). Posttranslational Protein Modifications: Current Implications for Cancer Detection, Prevention, and Therapeutics. Mol. Cell. Proteomics 5: 1799-1810 [Full Text]  
• Wang, M. Y., Lu, K. V., Zhu, S., Dia, E. Q., Vivanco, I., Shackleford, G. M., Cavenee, W. K., Mellinghoff, I. K., Cloughesy, T. F., Sawyers, C. L., Mischel, P. S. (2006). Mammalian Target of Rapamycin Inhibition Promotes Response to Epidermal Growth Factor Receptor Kinase Inhibitors in PTEN-Deficient and PTEN-Intact Glioblastoma Cells. Cancer Res. 66: 7864-7869 [Abstract] [Full Text]  
• Cloughesy, T. F., Wen, P. Y., Robins, H. I., Chang, S. M., Groves, M. D., Fink, K. L., Junck, L., Schiff, D., Abrey, L., Gilbert, M. R., Lieberman, F., Kuhn, J., DeAngelis, L. M., Mehta, M., Raizer, J. J., Yung, W.K. A., Aldape, K., Wright, J., Lamborn, K. R., Prados, M. D. (2006). Phase II Trial of Tipifarnib in Patients With Recurrent Malignant Glioma Either Receiving or Not Receiving Enzyme-Inducing Antiepileptic Drugs: A North American Brain Tumor Consortium Study. JCO 24: 3651-3656 [Abstract] [Full Text]  
• Wei, Q., Clarke, L., Scheidenhelm, D. K., Qian, B., Tong, A., Sabha, N., Karim, Z., Bock, N. A., Reti, R., Swoboda, R., Purev, E., Lavoie, J.-F., Bajenaru, M. L., Shannon, P., Herlyn, D., Kaplan, D., Henkelman, R. M., Gutmann, D. H., Guha, A. (2006). High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model.. Cancer Res. 66: 7429-7437 [Abstract] [Full Text]  
• Doherty, L., Gigas, D. C., Kesari, S., Drappatz, J., Kim, R., Zimmerman, J., Ostrowsky, L., Wen, P. Y. (2006). Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas.. Neurology 67: 156-158 [Abstract] [Full Text]  
• Yang, W., Barth, R. F., Wu, G., Kawabata, S., Sferra, T. J., Bandyopadhyaya, A. K., Tjarks, W., Ferketich, A. K., Moeschberger, M. L., Binns, P. J., Riley, K. J., Coderre, J. A., Ciesielski, M. J., Fenstermaker, R. A., Wikstrand, C. J. (2006). Molecular Targeting and Treatment of EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibody L8A4.. Clin. Cancer Res. 12: 3792-3802 [Abstract] [Full Text]  
• Baselga, J. (2006). Targeting Tyrosine Kinases in Cancer: The Second Wave.. Science 312: 1175-1178 [Abstract] [Full Text]  
• Gilbert, M. R. (2006). New treatments for malignant gliomas: careful evaluation and cautious optimism required.. ANN INTERN MED 144: 371-373 [Full Text]  
• Lassman, A. B., Abrey, L. E., Gilbert, M. R., Mellinghoff, I. K., Cloughesy, T., Mischel, P. S. (2006). Response of Glioblastomas to EGFR Kinase Inhibitors. NEJM 354: 525-526 [Full Text]  
• Stupp, R., Hegi, M. E., van den Bent, M. J., Mason, W. P., Weller, M., Mirimanoff, R. O., Cairncross, J. G., on behalf of the European Organisation for Researc, (2006). Changing paradigms--an update on the multidisciplinary management of malignant glioma.. The Oncologist 11: 165-180 [Abstract] [Full Text]