Cetuximab Insufficiently Inhibits Glioma Cell Growth Due to Persistent EGFR Downstream Signaling

REFERENCES

• Stupp, R.; Mason, W.P.; Van Den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; Curschmann, J.; Janzer, R.C.; Ludwin, S.K.; Gorlia, T.; Allgeier, A.; Lacombe, D.; Cairncross, J.G.; Eisenhauer, E.; Mirimanoff, R.O. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005, 352(10), 987–996.
   PubMed Web of Science ®Google Scholar
• Kleihues, P.; Ohgaki, H. Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro Oncol 1999, 1(1), 44–51.
   PubMedGoogle Scholar
• Kaur, B.; Tan, C.; Brat, D.J.; Post, D.E.; Van Meir, E.G. Genetic and hypoxic regulation of angiogenesis in gliomas. J Neuro Oncol 2004, 70(2), 229–243.
   PubMed Web of Science ®Google Scholar
• Kita, D.; Yonekawa, Y.; Weller, M.; Ohgaki, H. PIK3CA alterations in primary (de novo) and secondary glioblastomas. Acta Neuropathol (Berl) 2007, 113(3), 295–302.
   PubMed Web of Science ®Google Scholar
• Ekstrand, A.J.; James, C.D.; Cavenee, W.K.; Seliger, B.; Pettersson, R.F.; Collins, V.P. Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 1991, 51(8), 2164–2172.
   PubMed Web of Science ®Google Scholar
• Smith, J.S.; Tachibana, I.; Passe, S.M.; Huntley, B.K.; Borell, T.J.; Iturria, N.; O’Fallon, J.R.; Schaefer, P.L.; Scheithauer, B.W.; James, C.D.; Buckner, J.C.; Jenkins, R.B. PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 2001, 93(16), 1246–1256.
   PubMed Web of Science ®Google Scholar
• Wikstrand, C.J.; McLendon, R.E.; Friedman, A.H.; Bigner, D.D. Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII. Cancer Res 1997, 57(18), 4130–4140.
   PubMed Web of Science ®Google Scholar
• Alroy, I.; Yarden, Y. The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand–receptor interactions. FEBS Lett 1997, 410(1), 83–86.
   PubMed Web of Science ®Google Scholar
• Stokoe, D.; Stephens, L.R.; Copeland, T.; Gaffney, P.R.; Reese, C.B.; Painter, G.F.; Holmes, A.B.; McCormick, F.; Hawkins, P.T. Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 1997, 277(5325), 567–570.
   PubMed Web of Science ®Google Scholar
• Choe, G.; Horvath, S.; Cloughesy, T.F.; Crosby, K.; Seligson, D.; Palotie, A.; Inge, L.; Smith, B.L.; Sawyers, C.L.; Mischel, P.S. Analysis of the phosphatidylinositol 3′-kinase signaling pathway in glioblastoma patients in vivo. Cancer Res 2003, 63(11), 2742–2746.
   PubMed Web of Science ®Google Scholar
• Osaki, M.; Oshimura, M.; Ito, H. PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 2004, 9(6), 667–676.
   PubMed Web of Science ®Google Scholar
• Cunningham, D.; Humblet, Y.; Siena, S.; Khayat, D.; Bleiberg, H.; Santoro, A. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004, 351(4), 337–345.
   PubMed Web of Science ®Google Scholar
• Rocha-Lima, C.M.; Soares, H.P.; Raez, L.E.; Singal, R. EGFR targeting of solid tumors. Cancer Control 2007, 14(3), 295–304.
   PubMedGoogle Scholar
• Shirai, K.; O’Brien, P.E. Molecular targets in squamous cell carcinoma of the head and neck. Curr Treat Options Oncol 2007, 8(3), 239–251.
   PubMedGoogle Scholar
• 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.; Kao, J.C.; Stenzel, T.T.; Ahmed Rasheed, B.K.; Tourt-Uhlig, S.E.; Herndon, J.E.; Vredenburgh, J.J.; Sampson, J.H.; Friedman, A.H.; Bigner, D.D.; Friedman, H.S. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol 2004, 22(1), 133–142.
   PubMed Web of Science ®Google Scholar
• Quan, A.L.; Barnett, G.H.; Lee, S.Y.; Vogelbaum, M.A.; Toms, S.A.; Staugaitis, S.M.; Prayson, R.A.; Peereboom, D.M.; Stevens, G.H.; Cohen, B.H.; Suh, J.H. Epidermal growth factor receptor amplification does not have prognostic significance in patients with glioblastoma multiforme. Int J Radiat Oncol Biol Phys 2005, 63(3), 695–703.
   PubMed Web of Science ®Google Scholar
• Lassman, A.B.; Rossi, M.R.; Razier, J.R.; Abrey, L.E.; Lieberman, F.S.; Grefe, C.N.; Lamborn, K.; Pao, W.; Shih, A.H.; Kuhn, J.G.; Wilson, R.; Nowak, N.J.; Cowell, J.K.; DeAngelis, L.M.; Wen, P.; Gilbert, M.R.; Chang, S.; Yung, W.A.; Prados, M.; Holland, E.C. Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01. Clin Cancer Res 2005, 11(21), 7841–7850.
   PubMed Web of Science ®Google Scholar
• Franceschi, E.; Cavallo, G.; Lonardi, S.; Magrini, E.; Tosoni, A.; Grosso, D.; Scopece, L.; Blatt, V.; Urbini, B.; Pession, A.; Tallini, G.; Crino, L.; Brandes, A.A. Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Br J Cancer 2007, 96(7), 1047–1051.
   PubMed Web of Science ®Google Scholar
• Haas-Kogan, D.A.; Prados, M.D.; Tihan, T.; Eberhard, D.A.; Jelluma, N.; Arvold, N.D.; Baumber, R.; Lamborn, K.R.; Kapadia, A.; Malec, M.; Berger, M.S.; Stokoe, D. Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib. J Natl Cancer Inst 2005, 97(12), 880–887.
   PubMed Web of Science ®Google Scholar
• 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.; 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. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med 2005, 353(19), 2012–2024.
   PubMed Web of Science ®Google Scholar
• Liu, W.; James, C.D.; Frederick, L.; Alderete, B.E.; Jenkins, R.B. PTEN/MMAC1 mutations and EGFR amplification in glioblastomas. Cancer Res 1997, 57(23), 5254–5257.
   PubMed Web of Science ®Google Scholar
• Sano, T.; Lin, H.; Chen, X.; Langford, L.A.; Koul, D.; Bondy, M.L.; Hess, K.R.; Myers, J.N.; Hong, Y.K.; Yung, W.K.; Steck, P.A. Differential expression of MMAC/PTEN in glioblastoma multiforme: relationship to localization and prognosis. Cancer Res 1999, 59(8), 1820–1824.
   PubMed Web of Science ®Google Scholar
• Bianco, R.; Shin, I.; Ritter, C.A.; Yakes, F.M.; Basso, A.; Rosen, N.; Tsurutani, J.; Dennis, P.A.; Mills, G.B.; Arteaga, C.L. Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Oncogene 2003, 22(18), 2812–2822.
   PubMed Web of Science ®Google Scholar
• Mellinghoff, I.K.; Cloughesy, T.F.; Mischel, P.S. PTEN-mediated resistance to epidermal growth factor receptor kinase inhibitors. Clin Cancer Res 2007, 13(2 Pt 1), 378–381.
   PubMed Web of Science ®Google Scholar
• Li, S.; Schmitz, K.R.; Jeffrey, P.D.; Wiltzius, J.J.; Kussie, P.; Ferguson, K.M. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 2005, 7(4), 301–311.
   PubMed Web of Science ®Google Scholar
• Goldstein, N.I.; Prewett, M.; Zuklys, K.; Rockwell, P.; Mendelsohn, J. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin Cancer Res 1995, 1(11), 1311–1318.
   PubMed Web of Science ®Google Scholar
• Rivera, F.; Vega-Villegas, M.E.; Lopez-Brea, M.F. Cetuximab, its clinical use and future perspectives. Anticancer Drugs 2008, 19(2), 99–113.
   PubMed Web of Science ®Google Scholar
• Eller, J.L.; Longo, S.L.; Hicklin, D.J.; Canute, G.W. Activity of anti-epidermal growth factor receptor monoclonal antibody C225 against glioblastoma multiforme. Neurosurgery 2002, 51(4), 1005–1013.
   PubMed Web of Science ®Google Scholar
• Eller, J.L.; Longo, S.L.; Kyle, M.M.; Bassano, D.; Hicklin, D.J.; Canute, G.W. Anti-epidermal growth factor receptor monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo. Neurosurgery 2005, 56(1), 155–162.
   PubMed Web of Science ®Google Scholar
• Combs, S.E.; Schulz-Ertner, D.; Roth, W.; Herold-Mende, C.; Debus, J.; Weber, K.J. In vitro responsiveness of glioma cell lines to multimodality treatment with radiotherapy, temozolomide, and epidermal growth factor receptor inhibition with cetuximab. Int J Radiat Oncol Biol Phys 2007, 68(3), 873–882.
   PubMed Web of Science ®Google Scholar
• Filmus, J.; Pollak, M.N.; Cairncross, J.G.; Buick, R.N. Amplified, overexpressed and rearranged epidermal growth factor receptor gene in a human astrocytoma cell line. Biochem Biophys Res Commun 1985, 131(1), 207–215.
   PubMed Web of Science ®Google Scholar
• Huang, S.M.; Bock, J.M.; Harari, P.M. Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res 1999, 59(8), 1935–1940.
   PubMed Web of Science ®Google Scholar
• Ullrich, A.; Coussens, L.; Hayflick, J.S.; Dull, T.J.; Gray, A.; Tam, A.W.; Lee, J.; Yarden, Y.; Libermann, T.A.; Schlessinger, J. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 1984, 309(5967), 418–425.
   PubMed Web of Science ®Google Scholar
• Pandita, A.; Aldape, K.D.; Zadeh, G.; Guha, A.; James, C.D. Contrasting in vivo and in vitro fates of glioblastoma cell subpopulations with amplified EGFR. Genes Chromosomes Cancer 2004, 39(1), 29–36.
   PubMed Web of Science ®Google Scholar
• Ishii, N.; Maier, D.; Merlo, A.; Tada, M.; Sawamura, Y.; Diserens, A.C.; Van Meir, E.G. Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol 1999, 9(3), 469–479.
   PubMed Web of Science ®Google Scholar
• Sunada, H.; Magun, B.E.; Mendelsohn, J.; MacLeod, C.L. Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation. Proc Natl Acad Sci USA 1986, 83(11), 3825–3829.
   PubMed Web of Science ®Google Scholar
• Perez-Torres, M.; Guix, M.; Gonzalez, A.; Arteaga, C.L. Epidermal growth factor receptor (EGFR) antibody down-regulates mutant receptors and inhibits tumors expressing EGFR mutations. J Biol Chem 2006, 281(52), 40183–40192.
   PubMed Web of Science ®Google Scholar
• Jaramillo, M.L.; Leon, Z.; Grothe, S.; Paul-Roc, B.; Abulrob, A.; O’Connor, M.M. Effect of the anti-receptor ligand-blocking 225 monoclonal antibody on EGF receptor endocytosis and sorting. Exp Cell Res 2006, 312(15), 2778–2790.
   PubMed Web of Science ®Google Scholar
• Andersen, P.; Pedersen, M.W.; Woetmann, A.; Villingshoj, M.; Stockhausen, M.T.; Odum, N.; Poulsen, H.S. EGFR induces expression of IRF-1 via STAT1 and STAT3 activation leading to growth arrest of human cancer cells. Int J Cancer 2008, 122(2), 342–349.
   PubMed Web of Science ®Google Scholar
• Fukai, J.; Nishio, K.; Itakura, T.; Koizumi, F. Antitumor activity of cetuximab against malignant glioma cells overexpressing EGFR deletion mutant variant III. Cancer Sci 2008, 99(10), 2062–2069.
   PubMed Web of Science ®Google Scholar
• Lokker, N.A.; Sullivan, C.M.; Hollenbach, S.J.; Israel, M.A.; Giese, N.A. Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Cancer Res 2002, 62(13), 3729–3735.
   PubMed Web of Science ®Google Scholar
• Chakravarti, A.; Loeffler, J.S.; Dyson, N.J. Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res 2002, 62(1), 200–207.
   PubMed Web of Science ®Google Scholar
• Lievre, A.; Bachet, J.B.; Le Corre, D.; Boige, V.; Landi, B.; Emile, J.F.; Cote, J.F.; Tomasic, G.; Penna, C.; Ducreux, M.; Rougier, P.; Penault-Llorca, F.; Laurent-Puig, P. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006, 66(8), 3992–3995.
   PubMed Web of Science ®Google Scholar
• Lymbouridou, R.; Soufla, G.; Chatzinikola, A.M.; Vakis, A.; Spandidos, D.A. Down-regulation of K-ras and H-ras in human brain gliomas. Eur J Cancer 2009.
   PubMedGoogle Scholar
• Martens, T.; Laabs, Y.; Gunther, H.S.; Kemming, D.; Zhu, Z.; Witte, L.; Hagel, C.; Westphal, M.; Lamszus, K. Inhibition of glioblastoma growth in a highly invasive nude mouse model can be achieved by targeting epidermal growth factor receptor but not vascular endothelial growth factor receptor-2. Clin Cancer Res 2008, 14(17), 5447–5458.
   PubMed Web of Science ®Google Scholar
• Hasselbalch, B.; Lassen, U.; Hansen, S.; Holmberg, M.; Sorensen, M.; Kosteljanetz, M.; Broholm, H.; Stockhausen, M.T.; Poulsen, H.S. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial. Neuro Oncol 2010, 12(5), 508–516.
   PubMed Web of Science ®Google Scholar
• Vredenburgh, J.J.; Desjardins, A.; Herndon, J.E.; Marcello, J.; Reardon, D.A.; Quinn, J.A.; Rich, J.N.; Sathornsumetee, S.; Gururangan, S.; Sampson, J.; Wagner, M.; Bailey, L.; Bigner, D.D.; Friedman, A.H.; Friedman, H.S. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007, 25(30), 4722–4729.
   PubMed Web of Science ®Google Scholar
• Prados, M.D.; Lamborn, K.; Yung, W.K.; Jaeckle, K.; Robins, H.I.; Mehta, M.; Fine, H.A.; Wen, P.Y.; Cloughesy, T.; Chang, S.; Nicholas, M.K.; Schiff, D.; Greenberg, H.; Junck, L.; Fink, K.; Hess, K.; Kuhn, J. A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Neuro Oncol 2006, 8(2), 189–193.
   PubMed Web of Science ®Google Scholar
• Fan, Q.W.; Cheng, C.K.; Nicolaides, T.P.; Hackett, C.S.; Knight, Z.A.; Shokat, K.M.; Weiss, W.A. A dual phosphoinositide-3-kinase {alpha}/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma. Cancer Res 2007, 67(17), 7960–7965.
   PubMed Web of Science ®Google Scholar
• 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. Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 2007, 318(5848), 287–290.
   PubMed Web of Science ®Google Scholar
• Zandi, R.; Larsen, A.B.; Andersen, P.; Stockhausen, M.T.; Poulsen, H.S. Mechanisms for oncogenic activation of the epidermal growth factor receptor. Cell Signal 2007, 19(10), 2013–2023.
   PubMed Web of Science ®Google Scholar
• Doody, J.F.; Wang, Y.; Patel, S.N.; Joynes, C.; Lee, S.P.; Gerlak, J.; Rolser, R.L.; Li, Y.; Steiner, P.; Bassi, R.; Hicklin, D.J.; Hadari, Y.R. Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non small cell lung cancers. Mol Cancer Ther 2007, 6(10), 2642–2651.
   PubMed Web of Science ®Google Scholar
• Patel, D.; Lahiji, A.; Patel, S.; Franklin, M.; Jimenez, X.; Hicklin, D.J.; Kang, X. Monoclonal antibody cetuximab binds to and down-regulates constitutively activated epidermal growth factor receptor vIII on the cell surface. Anticancer Res 2007, 27(5A), 3355–3366.
   PubMed Web of Science ®Google Scholar