Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The EGFR inhibitors gefitinib and erlotinib have failed to demonstrate efficacy in GBM, largely as a consequence of persistent PI3K signaling due to PTEN loss and/or coactivation of other receptor tyrosine kinases.
“Despite the compelling nature of EGFR as a drug target in GBM, the EGFR inhibitors gefitinib and erlotinib have failed to demonstrate efficacy (9–11), in large part as a consequence of persistent PI3K signaling due to PTEN loss and/or coactivation of other receptor tyrosine kinases (9, 10, 12).”
From An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR–Dependent Pathway (2011) · cites this paper as [9]
The Abstract (page unavailable) reports that only 10–20% of patients respond to EGFR kinase inhibitors, but it also says a small subgroup benefits from gefitinib or erlotinib. The in vitro studies section (page unavailable) links PTEN loss to resistance, while noting both Akt-dependent and Akt-independent mechanisms. Our copy does not establish coactivation of other receptor tyrosine kinases as a cause of resistance, or show that persistent PI3K signaling largely explains the drugs’ limited efficacy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe U87, U87-EGFRvIII, U87-EGFR, U87-EGFR-PTEN, A431, LN229, T98, H1975 and HeLa cell lines have previously been reported.
“These cell lines have previously been reported (9, 29).”
From An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR–Dependent Pathway (2011) · cites this paper as [9]
The U87MG Model section (page unavailable) reports U87MG cells engineered to express EGFR or EGFRvIII, including PTEN-overexpressing cells. Other Cell-Line Models (page unavailable) reports A431 cells. Our copy does not report LN229, T98, H1975, or HeLa, so this source supports only part of the listed cell lines. (LLM, conf=0.88)
Experimental — accuracy not yet measuredClinical evidence suggests that the presence of EGFRvIII can predict clinical responses of GBMs to the EGFR TKIs gefitinib and erlotinib.
“There is clinical evidence suggesting that the presence of EGFRvIII can predict clinical responses of GBMs to the EGFR TKIs gefitinib and erlotinib (Haas-Kogan et al., 2005; Mellinghoff et al., 2005).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Mellinghoff et al., 2005
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486 · see citing works
<i>EGFR</i> Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368 · see citing works
Self-citationThe phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621 · see citing works
Druker, B. J., Talpaz, M., Resta, D. J., Peng, B., Buchdunger, E., Ford, J., Lydon, N., Kantarjian, H. M., Capdeville, R., Ohno-Jones, S., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441401 · Cited by 5,237 · see citing works
Self-citationLi, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785 · see citing works
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
Demetri, G. D., von Mehren, M., Blanke, C. D., Van den Abbeele, A. D., Eisenberg, B., Roberts, P. J., Heinrich, M. C., Tuveson, D. A., Singer, S., Janicek, M., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020461 · Cited by 4,389 · see citing works
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338 · see citing works
Fukuoka, M., Yano, S., Giaccone, G., Tamura, T., Nakagawa, K., Douillard, J., Nishiwaki, Y., Vansteenkiste, J., Kudoh, S., Rischin, D., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.10.038 · Cited by 2,871 · see citing works
Steck, P. A., Pershouse, M. A., Jasser, S. A., Yung, W. K. A., Lin, H., Ligon, A. H., Langford, L. A., Baumgard, M. L., Hattier, T., Davis, T., et al. (1997) · Nature Genetics · doi:10.1038/ng0497-356 · Cited by 2,742 · see citing works
Druker, B. J., Sawyers, C. L., Kantarjian, H., Resta, D. J., Reese, S. F., Ford, J. M., Capdeville, R., & Talpaz, M. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441402 · Cited by 2,713 · see citing works
Self-citationKris, M. G., Natale, R. B., Herbst, R. S., Lynch, Jr., Prager, D., Belani, C. P., Schiller, J. H., Kelly, K., Spiridonidis, H., Sandler, A., et al. (2003) · JAMA · doi:10.1001/jama.290.16.2149 · Cited by 2,517 · see citing works
A small molecule–kinase interaction map for clinical kinase inhibitors
Fabian, M. A., Biggs, W., Treiber, D. K., Atteridge, C. E., Azimioara, M. D., Benedetti, M. G., Carter, T. A., Ciceri, P., Edeen, P. T., Floyd, M. B., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1068 · Cited by 1,901 · see citing works
Addiction to Oncogenes--the Achilles Heal of Cancer
Weinstein, I. (2002) · Science · doi:10.1126/science.1073096 · Cited by 1,753 · see citing works
Gefitinib-Sensitizing EGFR Mutations in Lung Cancer Activate Anti-Apoptotic Pathways
Sordella, R., Bell, D. W., Haber, D. A., & Settleman, J. E. (2004) · Science · doi:10.1126/science.1101637 · Cited by 1,605 · see citing works
Assembly of Cell Regulatory Systems Through Protein Interaction Domains
Pawson, T. J., & Nash, P. (2003) · Science · doi:10.1126/science.1083653 · Cited by 1,403 · see citing works
van Oosterom, A. T., Judson, I. R., Verweij, J., Stroobants, S. G., Paola, E. D. D., Dimitrijević, S., Martens, M., Webb, A., Sciot, R., Glabbeke, M. M. V., et al. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06535-7 · Cited by 1,258 · see citing works
Holbro, T., Beerli, R. R., Maurer, F., Koziczak, M., Barbas, C. F., & Hynes, N. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1537685100 · Cited by 952 · see citing works
Structural alterations of the epidermal growth factor receptor gene in human gliomas.
Wong, A. J., Ruppert, J. M., Bigner, S. H., Grzeschik, C. H., Humphrey, P. A., Bigner, D. S., & Vogelstein, B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.7.2965 · Cited by 851 · see citing works
Intragenic ERBB2 kinase mutations in tumours
Stephens, P., Hunter, C., Bignell, G., Edkins, S., Davies, H., Teague, J., Stevens, C., O'Meara, S., Smith, R., Parker, A., et al. (2004) · Nature · doi:10.1038/431525b · Cited by 802 · see citing works
Phase II Trial of Gefitinib in Recurrent Glioblastoma
Rich, J. N., Reardon, D. A., Peery, T., Dowell, J. M., Quinn, J. A., Penne, K. L., Wikstrand, C. J., Van Duyn, L. B., Dancey, J. E., McLendon, R. E., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.110 · Cited by 734 · see citing works
Miller, V. A., Kris, M. G., Shah, N., Patel, J. D., Azzoli, C. G., Gomez, J. E., Krug, L. M., Pao, W. J., Rizvi, N. A., Pizzo, B., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.158 · Cited by 729 · see citing works
Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas.
Frederick, L. A., Wang, X. Y., Eley, G. D., & James, C. D. (2000) · PubMed · Cited by 661 · see citing works
Ekstrand, A. J., James, C. D., Cavenee, W. K., Seliger, B., Pettersson, R. F., & Collins, V. P. (1991) · PubMed · Cited by 630 · see citing works
Self-citationSmith, J. S., Tachibana, I., Passe, S. M., Huntley, B. K., Borell, T. J., Iturria, N. L., O'Fallon, J. R., Schaefer, P., Scheithauer, B. W., James, C. D., et al. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.16.1246 · Cited by 630 · see citing works
Huang, H., Nagane, M., Klingbeil, C. K., Lin, H., Nishikawa, R., Ji, X.-D., Huang, C., Gill, G. N., Wiley, H. S., & Cavenee, W. K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.5.2927 · Cited by 597 · see citing works
Self-citationSugawa, N., Ekstrand, A. J., James, C. D., & Collins, V. P. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.21.8602 · Cited by 594 · see citing works
Bianco, R., Shin, I., Ritter, C. A., Yakes, F. M., Basso, A., Rosen, N. X., Tsurutani, J., Dennis, P. A., Mills, G. B., & Arteaga, C. L. (2003) · Oncogene · doi:10.1038/sj.onc.1206388 · Cited by 449 · see citing works
Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain
Furnari, F. B., Lin, H., Huang, H., & Cavenee, W. K. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12479 · Cited by 437 · see citing works
Self-citationFurnari, F. B., Huang, H., & Cavenee, W. K. (1998) · PubMed · Cited by 399 · see citing works
Self-citationTyrosine kinase inhibitors: From rational design to clinical trials
Traxler, P. M., Bold, G., Buchdunger, E., Caravatti, G., Furet, P., Manley, P. W., O’Reilly, T., Wood, J. M., & Zimmermann, J. (2001) · Medicinal Research Reviews · doi:10.1002/med.1022 · Cited by 325 · see citing works
Somatic Mutations ofEGFRin Colorectal Cancers and Glioblastomas
Barber, T. D., Vogelstein, B., Kinzler, K. W., & Velculescu, V. E. (2004) · New England Journal of Medicine · doi:10.1056/nejm200412303512724 · Cited by 314 · see citing works
Liliental, J., Moon, S. Y., Lesche, R., Mamillapalli, R., Li, D., Zheng, Y., Sun, H., & Wu, H. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00417-6 · Cited by 290 · see citing works
Batra, S. K., Castelino‐Prabhu, S., Wikstrand, C. J., Zhu, X., Humphrey, P. A., Friedman, H. S., & Bigner, D. D. (1995) · PubMed · Cited by 281 · see citing works
Aldape, K., Ballman, K. V., Furth, A. F., Buckner, J. C., Giannini, C., Burger, P. C., Scheithauer, B. W., Jenkins, R. B., & James, C. D. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.7.700 · Cited by 275 · see citing works
Goudar, R. K., Shi, Q., Hjelmeland, M. D., Keir, S. T., McLendon, R. E., Wikstrand, C. J., Reese, E. D., Conrad, C. A., Traxler, P. M., Lane, H. A., et al. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.101.4.1 · Cited by 241 · see citing works
Self-citationSonoda, Y., Ozawa, T., Aldape, K. D., Deen, D. F., Berger, M. S., & Pieper, R. O. (2001) · PubMed · Cited by 224 · see citing works
Mishima, K., Johns, T. G., Luwor, R. B., et al. (2001) · PubMed · Cited by 207 · see citing works
Targeting epidermal growth factor receptor—are we missing the mark?
Dancey, J. E., & Freidlin, B. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13810-x · Cited by 192 · see citing works
Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival.
Ermoian, R. P., Furniss, C. S., Lamborn, K. R., Basila, D., Berger, M. S., GOTTSCHALK, A. R., Nicholas, M. K., Stokoe, D., & Haas-Kogan, D. A. (2002) · PubMed · Cited by 178 · see citing works
Self-citationOpportunities and challenges in the development of kinase inhibitor therapy for cancerPreprint
Sawyers, C. L. (2003) · Genes & Development · doi:10.1101/gad.1152403 · Cited by 170 · see citing works
Self-citationLi, B., Yuan, M., Kim, I.-A., Chang, C.-M., Bernhard, E. J., & Shu, H. G. (2004) · Oncogene · doi:10.1038/sj.onc.1207602 · Cited by 168 · see citing works
Hitting the Target: Emerging Technologies in the Search for Kinase Substrates
Manning, B. D., & Cantley, L. C. (2002) · Science Signaling · doi:10.1126/stke.2002.162.pe49 · Cited by 116 · see citing works
Han, Y., Caday, C. G., Nanda, A., et al. (1996) · PubMed · Cited by 111 · see citing works
Mellinghoff, I. K., Tran, C., & Sawyers, C. L. (2002) · PubMed · Cited by 88 · see citing works
Self-citationEGFR tyrosine kinase domain mutations in human gliomas
Marie, Y., Carpentier, A. F., Omuro, A. M. P., Sanson, M., Thillet, J., Hoang‐Xuan, K., & Delattre, J. (2005) · Neurology · doi:10.1212/01.wnl.0000158654.07080.b0 · Cited by 79 · see citing works
EGFRMutations and Sensitivity to Gefitinib
Rossi, G., Marchioni, A., & Longo, L. (2004) · New England Journal of Medicine · doi:10.1056/nejm200409163511221 · Cited by 73 · see citing works
33 Phase I study of OSI-774 alone or with temozolomide in patients with malignant glioma
Prados, M., Chang, S. M., Burton, E. M., Parney, I., Kapadia, A., Rabbitt, J. E., Page, M., Federoff, A., Kelley, S. K., & Fyfe, G. (2003) · European Journal of Cancer Supplements · doi:10.1016/s1359-6349(03)90067-x · Cited by 56 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- Choe G, Horvath S, Cloughesy TF, et al. Analysis of the phosphatidylinositol 3'- kinase signaling pathway in glioblastoma patients in vivo. Cancer Res 2003;63:2742-6.
- Batra SK, Castelino-Prabhu S, Wikstrand CJ, et al. Epidermal growth factor ligand- independent, unregulated, cell-transform- The New England Journal of Medicine Downloaded from nejm.org on August 29, 2023. For personal use only. No other uses without permission. Copyright © 2005 Massachusetts Medical Society. All rights reserved. n engl j med 353;19
- www.nejm.org november 10, 2005 2024 egfr kinase inhibitors for glioblastomas ing potential of a naturally occurring human mutant EGFRvIII gene. Cell Growth Differ 1995;6:1251-9.
Cited by
Sorted by citations
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857 · see citing works
Skog, J., Würdinger, T., van Rijn, S., Meijer, D. H., Gainche, L., Curry, W. T., Carter, B. S., Krichevsky, A. M., & Breakefield, X. O. (2008) · Nature Cell Biology · doi:10.1038/ncb1800 · Cited by 5,001 · see citing works
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445 · see citing works
Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.11.025 · Cited by 2,317 · see citing works
Engelman, J. A., Chen, L., Tan, X., Crosby, K., Guimaraes, A. R., Upadhyay, R., Maira, M., McNamara, K., Perera, S. A., Song, Y., et al. (2008) · Nature Medicine · doi:10.1038/nm.1890 · Cited by 1,330 · see citing works
Jacob, F., Salinas, R. D., Zhang, D. Y., Nguyen, P. T. T., Schnoll, J. G., Wong, S. Z. H., Thokala, R., Sheikh, S., Saxena, D., Prokop, S., et al. (2020) · Cell · doi:10.1016/j.cell.2019.11.036 · Cited by 1,149 · see citing works
Maira, S.-M., Stauffer, F., Brueggen, J., Furet, P., Schnell, C., Fritsch, C., Brachmann, S., Chène, P., De Pover, A., Schoemaker, K., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0017 · Cited by 1,134 · see citing works
Self-citationERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics
Arteaga, C. L., & Engelman, J. A. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.025 · Cited by 1,048 · see citing works
Wolf, A., Agnihotri, S., Micallef, J., Mukherjee, J., Sabha, N., Cairns, R., Hawkins, C., & Guha, A. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20101470 · Cited by 789 · see citing works
Horvath, S., Zhang, B., Carlson, M., Lu, K. V., Zhu, S., Felciano, R. M., Laurance, M. F., Zhao, W., Qi, S., Chen, Z., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608396103 · Cited by 641 · see citing works
Self-citationLaurent-Puig, P., Cayre, A., Manceau, G., Buc, E., Bachet, J.-B., Lecomte, T., Rougier, P., Lievre, A., Landi, B., Boige, V., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.21.6796 · Cited by 673 · see citing works
Targeting the cancer kinome through polypharmacology
Knight, Z. A., Lin, H., & Shokat, K. M. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2787 · Cited by 674 · see citing works
Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge
Sturm, D., Bender, S., Jones, D. T. W., Lichter, P., Grill, J., Becher, O., Hawkins, C., Majewski, J., Jones, C., Costello, J. F., et al. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3655 · Cited by 555 · see citing works
Sos, M. L., Koker, M., Weir, B. A., Heynck, S., Rabinovsky, R., Zander, T., Seeger, J. M., Weiss, J., Fischer, F., Frommolt, P., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4055 · Cited by 504 · see citing works
Guo, D., Reinitz, F., Youssef, M., Hong, C., Nathanson, D., Akhavan, D., Kuga, D., Amzajerdi, A. N., Soto, H., Zhu, S., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0102 · Cited by 452 · see citing works
“The U87MG/U87MGEGFRvIII model system has been used extensively to study the molecular effects of EGFRvIII on GBM (9, 13, 14, 29, 30) and has been shown to faithfully recapitulate key molecular features of a patient with amplified and overexpressed EGFRvIII, including enhanced PI3K pathway activation (13, 14, 29, 30).”
BackgroundMethodInfluentialSelf-citationExtracellular vesicles in neurodegenerative disease — pathogenesis to biomarkers
Thompson, A. G., Gray, E., Heman-Ackah, S. M., Mäger, I., Talbot, K., Andaloussi, S. E., Wood, M. J., & Turner, M. R. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.68 · Cited by 431 · see citing works
Identification of noninvasive imaging surrogates for brain tumor gene-expression modules
Diehn, M., Nardini, C., Wang, D. S., McGovern, S., Jayaraman, M., Liang, Y., Aldape, K., Cha, S., & Kuo, M. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801279105 · Cited by 440 · see citing works
She, Q.-B., Halilovic, E., Ye, Q., Zhen, W., Shirasawa, S., Sasazuki, T., Solit, D. B., & Rosen, N. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.05.023 · Cited by 400 · see citing works
EGFR family: Structure physiology signalling and therapeutic targets <sup>†</sup>
Burgess, A. W. (2008) · Growth Factors · doi:10.1080/08977190802312844 · Cited by 288 · see citing works
Kuo, M. D., Gollub, J., Sirlin, C. B., Ooi, C., & Chen, X. (2007) · Journal of Vascular and Interventional Radiology · doi:10.1016/j.jvir.2007.04.031 · Cited by 168 · see citing works
Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate
Stevens, M. M., Maire, C. L., Chou, N., Murakami, M. A., Knoff, D. S., Kikuchi, Y., Kimmerling, R. J., Liu, H., Haidar, S., Calistri, N. L., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3697 · Cited by 106 · see citing works
Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinoma
Neel, D. S., & Bivona, T. G. (2017) · npj Precision Oncology · doi:10.1038/s41698-017-0007-0 · Cited by 98 · see citing works
Liffers, K., Kolbe, K., Westphal, M., Lamszus, K., & Schulte, A. (2016) · Targeted Oncology · doi:10.1007/s11523-015-0372-y · Cited by 41 · see citing works
- Authors
- Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., Lu, K. V., Yoshimoto, K., Huang, J. H. Y., Chute, D. J., Riggs, B. L., Horvath, S., Liau, L. M., Cavenee, W. K., Rao, P. N., Beroukhim, R., Peck, T. C., Lee, J. C., Sellers, W. R., Stokoe, D., Prados, M., Cloughesy, T. F., Sawyers, C. L., & Mischel, P. S.
- Affiliations
- University of California, Los Angeles (US)
- Institute of Molecular Biology (BG)
- University of California, San Francisco (US)
- Harvard University (US)
- Broad Institute (US)
- Neurology, Inc (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Mellinghoff, Ingo K.
- Vivanco, Igor
- Haas-Kogan, Daphne A.
- Zhu, Shaojun
- Lu, Kan V.
- Yoshimoto, Koji
- Chute, Dennis J.
- Horvath, Steve
- Liau, Linda M.
- Cavenee, Webster K.
- Rao, P. Nagesh
- Beroukhim, Rameen
- Peck, Timothy C.
- Sellers, William R.
- Stokoe, David
- Prados, Michael
- Cloughesy, Timothy F.
- Sawyers, Charles L.
- Mischel, Paul S.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2005-11-10
- Volume
- 353
- Issue
- 19
- Pages
- 2012-2024
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2070705072
- Cited by
- 1,442
- References
- 47
- Citations by year
- 2026: 16 · 2025: 11 · 2024: 23 · 2023: 35 · 2022: 24 · 2021: 32 · 2020: 28 · 2019: 37 · 2018: 28 · 2017: 48 · 2016: 45 · 2015: 71 · 2014: 82 · 2013: 88 · 2012: 118
- FWCI
- 49.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Accelerate Brain Cancer Cure
- Ziering Family Foundation
- National Institutes of Health (1k08ns043147-01, 5f31gm067600-02)
- Genentech
- University of California, San Francisco
- National Cancer Institute (U01CA062399, CA097257, 5T32CA09056, R01CA108633, U01CA105695, CA 108633, CA 95616, CA 62399, CA105695, P01CA095616, T32CA009172, T32CA009056, P50CA097257)
- National Institute of General Medical Sciences (5F31GM067600)
- National Institute of Neurological Disorders and Stroke (NS43147, R01NS050151, NS 050151)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- glioblastoma, EGFR kinase inhibitors, EGFRvIII, PTEN, HER2/neu, erlotinib, recurrent malignant glioma, drug response, molecular determinants
- MeSH terms
- Erlotinib Hydrochloride, Gefitinib, Adult, Aged, Antineoplastic Agents, DNA, Neoplasm, Female, Gene Amplification, Glioblastoma, Humans, Male, Middle Aged, Mutation, Oligodendroglioma, Quinazolines, Signal Transduction, Gene Expression, Polymerase Chain Reaction, Gene Deletion, Sequence Analysis, DNA, Genes, erbB-2, Genes, erbB-1, Protein Kinase Inhibitors, PTEN Phosphohydrolase, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
