Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab

References

• Carpenter G, Lembach KJ, Morrison MM, Cohen S. Characterization of the binding of 125I-labeled epidermal growth factor to human fibroblasts. J Biol Chem 1975; 250:4297 - 4304
   PubMed Web of Science ®Google Scholar
• Carpenter G, King L Jr, Cohen S. Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro. Nature 1978; 276:409 - 410
   PubMed Web of Science ®Google Scholar
• Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, et al. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 1984; 309:418 - 425
   PubMed Web of Science ®Google Scholar
• Eckhart W, Hutchinson MA, Hunter T. An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates. Cell 1979; 18:925 - 933
   PubMed Web of Science ®Google Scholar
• Hunter T, Sefton BM. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci USA 1980; 77:1311 - 1315
   PubMed Web of Science ®Google Scholar
• Riedel H, Dull TJ, Schlessinger J, Ullrich A. A chimaeric receptor allows insulin to stimulate tyrosine kinase activity of epidermal growth factor receptor. Nature 1986; 324:68 - 70
   PubMed Web of Science ®Google Scholar
• Schlessinger J. Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci 1988; 13:443 - 447
   PubMed Web of Science ®Google Scholar
• Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2:127 - 137
   PubMed Web of Science ®Google Scholar
• Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005; 5:341 - 354
   PubMed Web of Science ®Google Scholar
• Klapper LN, Glathe S, Vaisman N, Hynes NE, Andrews GC, Sela M, et al. The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci USA 1999; 96:4995 - 5000
   PubMed Web of Science ®Google Scholar
• Singh AB, Harris RC. Autocrine, paracrine and juxtacrine signaling by EGFR ligands. Cell Signal 2005; 17:1183 - 1193
   PubMed Web of Science ®Google Scholar
• Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 2009; 9:463 - 475
   PubMed Web of Science ®Google Scholar
• Guy PM, Platko JV, Cantley LC, Cerione RA, Carraway KL 3rd. Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc Natl Acad Sci USA 1994; 91:8132 - 8136
   PubMed Web of Science ®Google Scholar
• Wallasch C, Weiss FU, Niederfellner G, Jallal B, Issing W, Ullrich A. Heregulin-dependent regulation of HER2/neu oncogenic signaling by heterodimerization with HER3. EMBO J 1995; 14:4267 - 4275
   PubMed Web of Science ®Google Scholar
• Sebolt-Leopold JS, Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 2004; 4:937 - 947
   PubMed Web of Science ®Google Scholar
• Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009; 9:550 - 562
   PubMed Web of Science ®Google Scholar
• Carpenter G, Ji Q. Phospholipase C-gamma as a signal-transducing element. Exp Cell Res 1999; 253:15 - 24
   PubMed Web of Science ®Google Scholar
• Spitaler M, Cantrell DA. Protein kinase C and beyond. Nat Immunol 2004; 5:785 - 790
   PubMed Web of Science ®Google Scholar
• Griner EM, Kazanietz MG. Protein kinase C and other diacylglycerol effectors in cancer. Nat Rev Cancer 2007; 7:281 - 294
   PubMed Web of Science ®Google Scholar
• Mackay HJ, Twelves CJ. Targeting the protein kinase C family: are we there yet?. Nat Rev Cancer 2007; 7:554 - 562
   PubMed Web of Science ®Google Scholar
• Marti U, Burwen SJ, Wells A, Barker ME, Huling S, Feren AM, et al. Localization of epidermal growth factor receptor in hepatocyte nuclei. Hepatology 1991; 13:15 - 20
   PubMed Web of Science ®Google Scholar
• Cao H, Lei ZM, Bian L, Rao CV. Functional nuclear epidermal growth factor receptors in human choriocarcinoma JEG-3 cells and normal human placenta. Endocrinology 1995; 136:3163 - 3172
   PubMed Web of Science ®Google Scholar
• Lin SY, Makino K, Xia W, Matin A, Wen Y, Kwong KY, et al. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol 2001; 3:802 - 808
   PubMed Web of Science ®Google Scholar
• Lo HW, Hsu SC, Hung MC. EGFR signaling pathway in breast cancers: from traditional signal transduction to direct nuclear translocalization. Breast Cancer Res Treat 2006; 95:211 - 218
   PubMed Web of Science ®Google Scholar
• Lo HW, Hung MC. Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival. Br J Cancer 2006; 94:184 - 188
   PubMed Web of Science ®Google Scholar
• Lo HW, Xia W, Wei Y, Ali-Seyed M, Huang SF, Hung MC. Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer. Cancer Res 2005; 65:338 - 348
   PubMed Web of Science ®Google Scholar
• Psyrri A, Yu Z, Weinberger PM, Sasaki C, Haffty B, Camp R, et al. Quantitative determination of nuclear and cytoplasmic epidermal growth factor receptor expression in oropharyngeal squamous cell cancer by using automated quantitative analysis. Clin Cancer Res 2005; 11:5856 - 5862
   PubMed Web of Science ®Google Scholar
• Xia W, Wei Y, Du Y, Liu J, Chang B, Yu YL, et al. Nuclear expression of epidermal growth factor receptor is a novel prognostic value in patients with ovarian cancer. Mol Carcinog 2009; 48:610 - 617
   PubMed Web of Science ®Google Scholar
• Lo HW, Hsu SC, Ali-Seyed M, Gunduz M, Xia W, Wei Y, et al. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell 2005; 7:575 - 589
   PubMed Web of Science ®Google Scholar
• Hsu SC, Hung MC. Characterization of a novel tripartite nuclear localization sequence in the EGFR family. J Biol Chem 2007; 282:10432 - 10440
   PubMed Web of Science ®Google Scholar
• Lo HW, Cao X, Zhu H, Ali-Osman F. Cyclooxygenase-2 is a novel transcriptional target of the nuclear EGFRSTAT3 and EGFRvIII-STAT3 signaling axes. Mol Cancer Res 2010; 8:232 - 245
   PubMed Web of Science ®Google Scholar
• Lo HW, Ali-Seyed M, Wu Y, Bartholomeusz G, Hsu SC, Hung MC. Nuclear-cytoplasmic transport of EGFR involves receptor endocytosis, importin beta1 and CRM1. J Cell Biochem 2006; 98:1570 - 1583
   PubMed Web of Science ®Google Scholar
• Liao HJ, Carpenter G. Role of the Sec61 translocon in EGF receptor trafficking to the nucleus and gene expression. Mol Biol Cell 2007; 18:1064 - 1072
   PubMed Web of Science ®Google Scholar
• Hanada N, Lo HW, Day CP, Pan Y, Nakajima Y, Hung MC. Co-regulation of B-Myb expression by E2F1 and EGF receptor. Mol Carcinog 2006; 45:10 - 17
   PubMed Web of Science ®Google Scholar
• Hung LY, Tseng JT, Lee YC, Xia W, Wang YN, Wu ML, et al. Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression. Nucleic Acids Res 2008; 36:4337 - 4351
   PubMed Web of Science ®Google Scholar
• Wang SC, Nakajima Y, Yu YL, Xia W, Chen CT, Yang CC, et al. Tyrosine phosphorylation controls PCNA function through protein stability. Nat Cell Biol 2006; 8:1359 - 1368
   PubMed Web of Science ®Google Scholar
• Dittmann K, Mayer C, Kehlbach R, Rodemann HP. Radiation-induced caveolin-1 associated EGFR internalization is linked with nuclear EGFR transport and activation of DNA-PK. Mol Cancer 2008; 7:69
   PubMed Web of Science ®Google Scholar
• Liao HJ, Carpenter G. Cetuximab/C225-induced intracellular trafficking of epidermal growth factor receptor. Cancer Res 2009; 69:6179 - 6183
   PubMed Web of Science ®Google Scholar
• Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Bio 2006; 7:505 - 516
   PubMed Web of Science ®Google Scholar
• Haglund K, Sigismund S, Polo S, Szymkiewicz I, Di Fiore PP, Dikic I. Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation. Nat Cell Biol 2003; 5:461 - 466
   PubMed Web of Science ®Google Scholar
• Mineo C, Gill GN, Anderson GW. Regulated migration of epidermal growth factor receptor from caveolae. J Biol Chem 1999; 274:30636 - 30643
   PubMed Web of Science ®Google Scholar
• Vieira AV, Lamaze C, Schmid SL. Control of EGF receptor signaling by clathrin-mediated endocytosis. Science 1996; 274:2086 - 2089
   PubMed Web of Science ®Google Scholar
• Yamabhai M, Anderson RGW. Second cysteine-rich region of epidermal growth factor receptor contains targeting information for caveolae/rafts. J Biol Chem 2002; 277:24843 - 24846
   PubMed Web of Science ®Google Scholar
• Soubeyran P, Kowanetz K, Szymkiewicz I, Langdon WY, Dikic I. Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors. Nature 2002; 416:183 - 187
   PubMed Web of Science ®Google Scholar
• de Melker AA, van der Horst G, Borst J. c-Cbl directs EGF receptors into an endocytic pathway that involves the ubiquitin-interacting motif of Eps15. J Cell Sci 2004; 117:5001 - 5012
   PubMed Web of Science ®Google Scholar
• Marmor MD, Yarden Y. Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases. Oncogene 2004; 23:2057 - 2070
   PubMed Web of Science ®Google Scholar
• Bache KG, Slagsvold T, Stenmark H. Defective down-regulation of receptor tyrosine kinases in cancer. EMBO J 2004; 23:2707 - 2712
   PubMed Web of Science ®Google Scholar
• Hendriks BS, Opresko LK, Wiley HS, Lauffenburger D. Coregulation of epidermal growth factor receptor/human epidermal growth factor receptor 2 (HER2) levels and locations: Quantitative analysis of HER2 overexpression effects. Cancer Res 2003; 63:1130 - 1137
   PubMed Web of Science ®Google Scholar
• Worthylake R, Opresko LK, Wiley HS. ErbB-2 amplification inhibits downregulation and induces constitutive activation of both ErbB-2 and epidermal growth factor receptors. J Biol Chem 1999; 274:8865 - 8874
   PubMed Web of Science ®Google Scholar
• Baulida J, Kraus MH, Alimandi M, DiFiore PP, Carpenter G. All ErbB receptors other than the epidermal growth factor receptor are endocytosis impaired. J Biol Chem 1996; 271:5251 - 5257
   PubMed Web of Science ®Google Scholar
• Sorkin A, Waters CM. Endocytosis of growth-factor receptors. Bioessays 1993; 15:375 - 382
   PubMed Web of Science ®Google Scholar
• Wang ZX, Zhang LF, Yeung TK, Chen XM. Endocytosis deficiency of epidermal growth factor (EGF) receptor-ErbB2 heterodimers in response to EGF stimulation. Mol Biol Cell 1999; 10:1621 - 1636
   PubMed Web of Science ®Google Scholar
• Chung BM, Raja SM, Clubb RJ, Tu C, George M, Band V, et al. Aberrant trafficking of NSCLCassociated EGFR mutants through the endocytic recycling pathway promotes interaction with Src@. Bmc Cell Biol 2009; In press
   PubMed Web of Science ®Google Scholar
• Hendriks BS, Wiley HS, Lauffenburger D. HER2-mediated effects on EGFR endosomal sorting: Analysis of biophysical mechanisms. Biophys J 2003; 85:2732 - 45
   PubMed Web of Science ®Google Scholar
• Weichselbaum RR, Dunphy EJ, Beckett MA, Tybor AG, Moran WJ, Goldman ME, et al. Epidermal growth factor receptor gene amplification and expression in head and neck cancer cell lines. Head Neck 1989; 11:437 - 442
   PubMed Web of Science ®Google Scholar
• Veale D, Ashcroft T, Marsh C, Gibson GJ, Harris AL. Epidermal growth factor receptors in non-small cell lung cancer. Br J Cancer 1987; 55:513 - 516
   PubMed Web of Science ®Google Scholar
• Libermann TA, Razon N, Bartal AD, Yarden Y, Schlessinger J, Soreq H. Expression of epidermal growth factor receptors in human brain tumors. Cancer Res 1984; 44:753 - 760
   PubMed Web of Science ®Google Scholar
• Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 1985; 313:144 - 147
   PubMed Web of Science ®Google Scholar
• Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, et al. Amplification and overexpression of the EGF receptor gene in primary human glioblastomas. J Cell Sci Suppl 1985; 3:161 - 172
   PubMedGoogle Scholar
• Maurizi M, Almadori G, Ferrandina G, Distefano M, Romanini ME, Cadoni G, et al. Prognostic significance of epidermal growth factor receptor in laryngeal squamous cell carcinoma. Br J Cancer 1996; 74:1253 - 1257
   PubMed Web of Science ®Google Scholar
• FischerColbrie J, Witt A, Heinzl H, Speiser P, Czerwenka K, Sevelda P, et al. EGFR and steroid receptors in ovarian carcinoma: Comparison with prognostic parameters and outcome of patients. Anticancer Res 1997; 17:613 - 619
   PubMed Web of Science ®Google Scholar
• Kersemaekers AMF, Fleuren GJ, Kenter EG, Van den Broek LJCM, Uljee SM, Hermans J, et al. Oncogene alterations in carcinomas of the uterine cervix: Overexpression of the epidermal growth factor receptor is associated with poor prognosis. Clin Cancer Res 1999; 5:577 - 586
   PubMed Web of Science ®Google Scholar
• Mellon K, Wright C, Kelly P, Horne CHW, Neal DE. Long-term outcome related to epidermal growth-factor receptor status in bladder-cancer. Journal of Urology 1995; 153:919 - 925
   PubMed Web of Science ®Google Scholar
• Inada S, Koto T, Futami K, Arima S, Iwashita A. Evaluation of malignancy and the prognosis of esophageal cancer based on an immunohistochemical study (p53, E-cadherin, epidermal growth factor receptor). Surg Today 1999; 29:493 - 503
   PubMed Web of Science ®Google Scholar
• Ohgaki H, Watanabe K, Tachibana O, Sato K, Kleihues P. Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. J Neuropathol Exp Neurol 1996; 55:3
   Web of Science ®Google Scholar
• Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer 2001; 37:9 - 15
   PubMed Web of Science ®Google Scholar
• Nielsen JS, Jakobsen E, Holund B, Bertelsen K, Jakobsen A. Prognostic significance of p53, Her-2 and EGFR overexpression in borderline and epithelial ovarian cancer. Int J Gynecol Cancer 2004; 14:1086 - 1096
   PubMed Web of Science ®Google Scholar
• Santini J, Formento JL, Francoual M, Milano G, Schneider M, Dassonville O, et al. Characterization, quantification and potential clinical-value of the epidermal growth-factor receptor in head and neck squamous-cell carcinomas. Head Neck 1991; 13:132 - 139
   PubMed Web of Science ®Google Scholar
• Yasui W, Sumiyoshi H, Hata J, Kameda T, Ochiai A, Ito H, et al. Expression of epidermal growth-factor receptor in human gastric and colonic carcinomas. Cancer Res 1988; 48:137 - 141
   PubMed Web of Science ®Google Scholar
• Piyathilake CJ, Frost AR, Manne U, Weiss H, Bell WC, Heimburger DC, et al. Differential expression of growth factors in squamous cell carcinoma and pre-cancerous lesions of the lung. Clin Cancer Res 2002; 8:734 - 744
   PubMed Web of Science ®Google Scholar
• Scambia G, Panici PB, Ferrandina G, Battaglia F, Distefano M, Dandrea G, et al. Significance of epidermal growth-factor receptor expression in primary human endometrial cancer. Int J Cancer 1994; 56:26 - 30
   PubMed Web of Science ®Google Scholar
• Nicholson RI, Gee JMW, Harper ME. EGFR and cancer prognosis. Eur J Cancer 2001; 37:9 - 15
   PubMed Web of Science ®Google Scholar
• Sizeland AM, Burgess AW. Anti-sense transforming growth factor alpha oligonucleotides inhibit autocrine stimulated proliferation of a colon carcinoma cell line. Mol Biol Cell 1992; 3:1235 - 1243
   PubMed Web of Science ®Google Scholar
• Humphrey PA, Wong AJ, Vogelstein B, Zalutsky MR, Fuller GN, Archer GE, et al. Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma. Proc Natl Acad Sci USA 1990; 87:4207 - 4211
   PubMed Web of Science ®Google Scholar
• Malden LT, Novak U, Kaye AH, Burgess AW. Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme. Cancer Res 1988; 48:2711 - 2714
   PubMed Web of Science ®Google Scholar
• Peschard P, Park M. Escape from Cbl-mediated down-regulation: a recurrent theme for oncogenic deregulation of receptor tyrosine kinases. Cancer Cell 2003; 3:519 - 523
   PubMed Web of Science ®Google Scholar
• Gill GN, Kawamoto T, Cochet C, Le A, Sato JD, Masui H, et al. Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity. J Biol Chem 1984; 259:7755 - 7760
   PubMed Web of Science ®Google Scholar
• Kawamoto T, Sato JD, Le A, Polikoff J, Sato GH, Mendelsohn J. Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc Natl Acad Sci USA 1983; 80:1337 - 1341
   PubMed Web of Science ®Google Scholar
• Sato JD, Kawamoto T, Le AD, Mendelsohn J, Polikoff J, Sato GH. Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol Biol Med 1983; 1:511 - 529
   PubMedGoogle Scholar
• Masui H, Kawamoto T, Sato JD, Wolf B, Sato G, Mendelsohn J. Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res 1984; 44:1002 - 1007
   PubMed Web of Science ®Google Scholar
• Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 2005; 7:301 - 311
   PubMed Web of Science ®Google Scholar
• Yang XD, Jia XC, Corvalan JRF, Wang P, Davis CG. Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hemat 2001; 38:17 - 23
   PubMed Web of Science ®Google Scholar
• Sunada H, Magun BE, Mendelsohn J, MacLeod CL. Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation. Proc Natl Acad Sci USA 1986; 83:3825 - 3829
   PubMed Web of Science ®Google Scholar
• Goldstein NI, 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; 1:1311 - 1318
   PubMed Web of Science ®Google Scholar
• Sunada H, Magun BE, Mendelsohn J, Macleod CL. Monoclonal-antibody against epidermal growth-factor receptor is internalized without stimulating receptor phosphorylation. Proc Natl Acad Sci USA 1986; 83:3825 - 3829
   PubMed Web of Science ®Google Scholar
• Huang SM, Bock JM, Harari PM. Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res 1999; 59:1935 - 1940
   PubMed Web of Science ®Google Scholar
• Peng D, Fan Z, Lu Y, DeBlasio T, Scher H, Mendelsohn J. Anti-epidermal growth factor receptor monoclonal antibody 225 upregulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145. Cancer Res 1996; 56:3666 - 3669
   PubMed Web of Science ®Google Scholar
• Wu X, Rubin M, Fan Z, DeBlasio T, Soos T, Koff A, et al. Involvement of p27KIP1 in G1 arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody. Oncogene 1996; 12:1397 - 403
   PubMed Web of Science ®Google Scholar
• Baselga J. The EGFR as a target for anticancer therapy—focus on cetuximab. Eur J Cancer 2001; 37:16 - 22
   PubMed Web of Science ®Google Scholar
• P OC, Rhys-Evans P, Modjtahedi H, Court W, Box G, Eccles S. Overexpression of epidermal growth factor receptor in human head and neck squamous carcinoma cell lines correlates with matrix metalloproteinase-9 expression and in vitro invasion. Int J Cancer 2000; 86:307 - 317
   PubMed Web of Science ®Google Scholar
• P Oc, Rhys-Evans P, Court WJ, Box GM, Eccles SA. Differential modulation of proliferation, matrix metalloproteinase expression and invasion of human head and neck squamous carcinoma cells by c-erbB ligands. Clin Exp Metastasis 1999; 17:631 - 639
   PubMed Web of Science ®Google Scholar
• Bruns CJ, Harbison MT, Davis DW, Portera CA, Tsan R, McConkey DJ, et al. Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin Cancer Res 2000; 6:1936 - 1948
   PubMed Web of Science ®Google Scholar
• Perrotte P, Matsumoto T, Inoue K, Kuniyasu H, Eve BY, Hicklin DJ, et al. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin Cancer Res 1999; 5:257 - 265
   PubMed Web of Science ®Google Scholar
• Tortora G, Caputo R, Pomatico G, Pepe S, Bianco AR, Agrawal S, et al. Cooperative inhibitory effect of novel mixed backbone oligonucleotide targeting protein kinase A in combination with docetaxel and anti-epidermal growth factor-receptor antibody on human breast cancer cell growth. Clin Cancer Res 1999; 5:875 - 881
   PubMed Web of Science ®Google Scholar
• Liu B, Fang M, Schmidt M, Lu Y, Mendelsohn J, Fan Z. Induction of apoptosis and activation of the caspase cascade by anti-EGF receptor monoclonal antibodies in DiFi human colon cancer cells do not involve the c-jun N-terminal kinase activity. Br J Cancer 2000; 82:1991 - 1999
   PubMed Web of Science ®Google Scholar
• Mandal M, Adam L, Mendelsohn J, Kumar R. Nuclear targeting of Bax during apoptosis in human colorectal cancer cells. Oncogene 1998; 17:999 - 1007
   PubMed Web of Science ®Google Scholar
• Wu X, Fan Z, Masui H, Rosen N, Mendelsohn J. Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J Clin Invest 1995; 95:1897 - 1905
   PubMed Web of Science ®Google Scholar
• Kurai J, Chikumi H, Hashimoto K, Yamaguchi K, Yamasaki A, Sako T, et al. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin Cancer Res 2007; 13:1552 - 1561
   PubMed Web of Science ®Google Scholar
• Kimura H, Sakai K, Arao T, Shimoyama T, Tamura T, Nishio K. Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci 2007; 98:1275 - 1280
   PubMed Web of Science ®Google Scholar
• Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 2005; 23:1803 - 1810
   PubMed Web of Science ®Google Scholar
• Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007; 357:2040 - 2048
   PubMed Web of Science ®Google Scholar
• Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26:2311 - 2319
   PubMed Web of Science ®Google Scholar
• Borner M, Koeberle D, Von Moos R, Saletti P, Rauch D, Hess V, et al. Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK. Ann Oncol 2008; 19:1288 - 1292
   PubMed Web of Science ®Google Scholar
• Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, et al. Fluorouracil, leucovorin and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2009; 27:663 - 671
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360:1408 - 1417
   PubMed Web of Science ®Google Scholar
• Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008; 359:1116 - 1127
   PubMed Web of Science ®Google Scholar
• Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006; 354:567 - 578
   PubMed Web of Science ®Google Scholar
• Herbst RS, Arquette M, Shin DM, Dicke K, Vokes EE, Azarnia N, et al. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol 2005; 23:5578 - 5587
   PubMed Web of Science ®Google Scholar
• Baselga J, Trigo JM, Bourhis J, Tortochaux J, Cortes-Funes H, Hitt R, et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2005; 23:5568 - 5577
   PubMed Web of Science ®Google Scholar
• Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an eastern Cooperative Oncology Group study. J Clin Oncol 2005; 23:8646 - 8654
   PubMed Web of Science ®Google Scholar
• Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337 - 345
   PubMed Web of Science ®Google Scholar
• Robert F, Ezekiel MP, Spencer SA, Meredith RF, Bonner JA, Khazaeli MB, et al. Phase I study of antiepidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. J Clin Oncol 2001; 19:3234 - 3243
   PubMed Web of Science ®Google Scholar
• Thienelt CD, Bunn PA Jr, Hanna N, Rosenberg A, Needle MN, Long ME, et al. Multicenter phase I/II study of cetuximab with paclitaxel and carboplatin in untreated patients with stage IV non-small-cell lung cancer. J Clin Oncol 2005; 23:8786 - 8793
   PubMed Web of Science ®Google Scholar
• Rosell R, Robinet G, Szczesna A, Ramlau R, Constenla M, Mennecier BC, et al. Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Ann Oncol 2008; 19:362 - 369
   PubMed Web of Science ®Google Scholar
• Robert F, Blumenschein G, Herbst RS, Fossella FV, Tseng J, Saleh MN, et al. Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naive advanced non-small-cell lung cancer. J Clin Oncol 2005; 23:9089 - 9096
   PubMed Web of Science ®Google Scholar
• Herbst RS, Chansky K, Kelly K, Atkins JN, Davies AM, Dakhil SR, et al. phase II randomized selection trial evaluating concurrent chemotherapy plus cetuximab or chemotherapy followed by cetuximab in patients with advanced non-small cell lung cancer (NSCLC): Final report of SWOG 0342 2007; ASCO
   Google Scholar
• Butts CA, Bodkin D, Middleman EL, Englund CW, Ellison D, Alam Y, et al. Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer. J Clin Oncol 2007; 25:5777 - 5784
   PubMed Web of Science ®Google Scholar
• Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 2009; 373:1525 - 1531
   PubMed Web of Science ®Google Scholar
• Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, et al. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol 2010; 28:911 - 917
   PubMed Web of Science ®Google Scholar
• Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 2004; 101:13306 - 13311
   PubMed Web of Science ®Google Scholar
• Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350:2129 - 2139
   PubMed Web of Science ®Google Scholar
• Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304:1497 - 1500
   PubMed Web of Science ®Google Scholar
• Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005; 2:73
   PubMed Web of Science ®Google Scholar
• Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005; 352:786 - 792
   PubMed Web of Science ®Google Scholar
• Tsuchihashi Z, Khambata-Ford S, Hanna N, Janne PA. Responsiveness to cetuximab without mutations in EGFR. N Engl J Med 2005; 353:208 - 209
   PubMed Web of Science ®Google Scholar
• Mukohara T, Engelman JA, Hanna NH, Yeap BY, Kobayashi S, Lindeman N, et al. Differential effects of gefitinib and cetuximab on non-small-cell lung cancers bearing epidermal growth factor receptor mutations. J Natl Cancer Inst 2005; 97:1185 - 1194
   PubMed Web of Science ®Google Scholar
• Moroni M, Veronese S, Benvenuti S, Marrapese G, Sartore-Bianchi A, Di Nicolantonio F, et al. Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 2005; 6:279 - 286
   PubMed Web of Science ®Google Scholar
• Frattini M, Saletti P, Romagnani E, Martin V, Molinari F, Ghisletta M, et al. PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer 2007; 97:1139 - 1145
   PubMed Web of Science ®Google Scholar
• Personeni N, Fieuws S, Piessevaux H, De Hertogh G, De Schutter J, Biesmans B, et al. Clinical usefulness of EGFR gene copy number as a predictive marker in colorectal cancer patients treated with cetuximab: a fluorescent in situ hybridization study. Clin Cancer Res 2008; 14:5869 - 5876
   PubMed Web of Science ®Google Scholar
• Cappuzzo F, Finocchiaro G, Rossi E, Janne PA, Carnaghi C, Calandri C, et al. EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients. Ann Oncol 2008; 19:717 - 723
   PubMed Web of Science ®Google Scholar
• Sartore-Bianchi A, Moroni M, Veronese S, Carnaghi C, Bajetta E, Luppi G, et al. Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. J Clin Oncol 2007; 25:3238 - 3245
   PubMed Web of Science ®Google Scholar
• Hirsch FR, Herbst RS, Olsen C, Chansky K, Crowley J, Kelly K, et al. Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy. J Clin Oncol 2008; 26:3351 - 3357
   PubMed Web of Science ®Google Scholar
• Khambata-Ford S, Harbison CT, Hart LL, Awad M, Xu LA, Horak CE, et al. Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol 2010; 28:918 - 927
   PubMed Web of Science ®Google Scholar
• Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 2007; 25:3230 - 3237
   PubMed Web of Science ®Google Scholar
• Trahey M, McCormick F. A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants. Science 1987; 238:542 - 545
   PubMed Web of Science ®Google Scholar
• Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 2007; 7:295 - 308
   PubMed Web of Science ®Google Scholar
• Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006; 66:3992 - 3995
   PubMed Web of Science ®Google Scholar
• Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 2007; 96:1166 - 1169
   PubMed Web of Science ®Google Scholar
• De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 2008; 19:508 - 515
   PubMed Web of Science ®Google Scholar
• Punt CJ, Tol J, Rodenburg CJ, Cats A, Creemers GM, Schrama JG, et al. Randomized phase III study of capecitabine, oxaliplatin and bevacizumab with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG) 2008; ASCO Meeting Abstracts May 20 2008
   Google Scholar
• Van Cutsem E, Lang I, D'haens G, Moiseyenko V, Zaluski J, Folprecht G, et al. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience. ASCO Meeting Abstracts 2008; 2:2008
   Google Scholar
• Bokemeyer C, Bondarenko I, Hartmann J, De Braud F, Volovat C, Nippgen L, et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: The OPUS experience. ASCO Meeting Abstracts 2008; 4000
   Google Scholar
• Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359:1757 - 1765
   PubMed Web of Science ®Google Scholar
• Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26:1626 - 1634
   PubMed Web of Science ®Google Scholar
• Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 2009; 27:2091 - 2096
   PubMed Web of Science ®Google Scholar
• Loupakis F, Pollina L, Stasi I, Ruzzo A, Scartozzi M, Santini D, et al. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J Clin Oncol 2009; 27:2622 - 2629
   PubMed Web of Science ®Google Scholar
• Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, et al. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to antiepidermal growth factor receptor antibody therapies. Cancer Res 2007; 67:2643 - 2648
   PubMed Web of Science ®Google Scholar
• Marais R, Light Y, Paterson HF, Marshall CJ. Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation. EMBO J 1995; 14:3136 - 3145
   PubMed Web of Science ®Google Scholar
• Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 2007; 26:3291 - 3310
   PubMed Web of Science ®Google Scholar
• Niault TS, Baccarini M. Targets of Raf in tumorigenesis. Carcinogenesis 2010; 31:1165 - 1174
   PubMed Web of Science ®Google Scholar
• Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 2008; 26:5705 - 5712
   PubMed Web of Science ®Google Scholar
• Blanco R, Iwakawa R, Tang M, Kohno T, Angulo B, Pio R, et al. A gene-alteration profile of human lung cancer cell lines. Hum Mutat 2009; 30:1199 - 1206
   PubMed Web of Science ®Google Scholar
• Pratilas CA, Taylor BS, Ye Q, Viale A, Sander C, Solit DB, et al. (V600E)BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci USA 2009; 106:4519 - 4524
   PubMed Web of Science ®Google Scholar
• Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R, et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 2002; 62:6997 - 7000
   PubMed Web of Science ®Google Scholar
• Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417:949 - 954
   PubMed Web of Science ®Google Scholar
• Weber A, Langhanki L, Sommerer F, Markwarth A, Wittekind C, Tannapfel A. Mutations of the BRAF gene in squamous cell carcinoma of the head and neck. Oncogene 2003; 22:4757 - 4759
   PubMed Web of Science ®Google Scholar
• Perrone F, Suardi S, Pastore E, Casieri P, Orsenigo M, Caramuta S, et al. Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma. Clin Cancer Res 2006; 12:6643 - 6651
   PubMed Web of Science ®Google Scholar
• Fei Huang LAX, Khambata-Ford Shirin. Analysis of the correlation between gene expression of IGF-pathway components and benefit from cetuximab (Erbitux™) in metastatic colorectal cancer patients. AACR meeting Abstracts 2010;
   Google Scholar
• Perrotte P, Matsumoto T, Inoue K, Kuniyasu H, Eve BY, Hicklin DJ, et al. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin Cancer Res 1999; 5:257 - 265
   PubMed Web of Science ®Google Scholar
• Petit AMV, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, et al. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases downregulate vascular endothelial growth factor production by tumor cells in vitro and in vivo—Angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 1997; 151:1523 - 1530
   PubMed Web of Science ®Google Scholar
• Ciardiello F, Bianco R, Damiano V, Fontanini G, Caputo R, Pomatico G, et al. Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells. Clin Cancer Res 2000; 6:3739 - 3747
   PubMed Web of Science ®Google Scholar
• Viloria-Petit A, Crombet T, Jothy S, Hicklin D, Bohlen P, Schlaeppi JM, et al. Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: A role for altered tumor angiogenesis. Cancer Res 2001; 61:5090 - 5101
   PubMed Web of Science ®Google Scholar
• Ferrara N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat 1995; 36:127 - 137
   PubMed Web of Science ®Google Scholar
• Fontanini G, Vignati S, Boldrini L, Chine S, Silvestri V, Lucchi M, et al. Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma. Clin Cancer Res 1997; 3:861 - 865
   PubMed Web of Science ®Google Scholar
• Jung YD, Mansfield PF, Akagi M, Takeda A, Liu W, Bucana CD, et al. Effects of combination anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model. Eur J Cancer 2002; 38:1133 - 1140
   PubMed Web of Science ®Google Scholar
• Ciardiello F, Bianco R, Caputo R, Caputo R, Damiano V, Troiani T, et al. Antitumor activity of ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in human cancer cells with acquired resistance to antiepidermal growth factor receptor therapy. Clin Cancer Res 2004; 10:784 - 793
   PubMed Web of Science ®Google Scholar
• Bianco R, Rosa R, Damiano V, Daniele G, Gelardi T, Garofalo S, et al. Vascular endothelial growth factor receptor-1 contributes to resistance to anti-epidermal growth factor receptor drugs in human cancer cells. Clin Cancer Res 2008; 14:5069 - 5080
   PubMed Web of Science ®Google Scholar
• Lu Y, Li XQ, Liang K, Luwor R, Siddik ZH, Nuiis GB, et al. Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the Anti-EGFR monoclonal antibody cetuximab. Cancer Res 2007; 67:8240 - 8247
   PubMed Web of Science ®Google Scholar
• Bao J, Gur G, Yarden Y. Src promotes destruction of c-Cbl: Implications for oncogenic synergy between Src and growth factor receptors. Proc Natl Acad Sci USA 2003; 100:2438 - 2443
   PubMed Web of Science ®Google Scholar
• Wheeler DL, Huang S, Kruser TJ, Nechrebecki MM, Armstrong EA, Benavente S, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene 2008; 27:3944 - 3956
   PubMed Web of Science ®Google Scholar
• Grovdal LM, Stang E, Sorkin A, Madshus IH. Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradation. Exp Cell Res 2004; 300:388 - 395
   PubMed Web of Science ®Google Scholar
• Demory ML, Boerner JL, Davidson R, Faust W, Miyake T, Lee I, et al. Epidermal growth factor receptor translocation to the mitochondria: regulation and effect. J Biol Chem 2009; 284:36592 - 36604
   PubMed Web of Science ®Google Scholar
• Lo HW, Cao X, Zhu H, Ali-Osman F. Constitutively Activated STAT3 Frequently Coexpresses with Epidermal Growth Factor Receptor in High-Grade Gliomas and Targeting STAT3 Sensitizes Them to Iressa and Alkylators. Clin Cancer Res 2008; 14:6042 - 6054
   PubMedGoogle Scholar
• Lo HW, Hsu SC, Hung MC. EGFR signaling pathway in breast cancers: from traditional signal transduction to direct nuclear translocalization. Breast Cancer Res Tr 2006; 95:211 - 218
   PubMed Web of Science ®Google Scholar
• Lo HW, Hsu SC, Ali-Seyed M, Gunduz M, Xia WY, Wei YK, et al. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell 2005; 7:575 - 589
   PubMed Web of Science ®Google Scholar
• Lo HW, Ali-Seyed M, Wu Y, Bartholomeusz G, Hsu SC, Hung MC. Nuclear-cytoplasmic transport of EGFR involves receptor endocytosis, importin beta1 and CRM1. J Cell Biochem 2006; 98:1570 - 1583
   PubMed Web of Science ®Google Scholar
• Hanada N, Lo HW, Day CP, Pan Y, Nakajima Y, Hung MC. Co-regulation of B-Myb expression by E2F1 and EGF receptor. Mol Carcinogen 2006; 45:10 - 17
   PubMed Web of Science ®Google Scholar
• Kim J, Jahng WJ, Di Vizio D, Lee JS, Jhaveri R, Rubin MA, et al. The phosphoinositide kinase PIKfyve mediates epidermal growth factor receptor trafficking to the nucleus. Cancer Res 2007; 67:9229 - 37
   PubMed Web of Science ®Google Scholar
• Xia WY, Wei YK, Du Y, Liu JS, Chang B, Yu YL, et al. Nuclear expression of epidermal growth factor receptor is a novel prognostic value in patients with ovarian cancer. Mol Carcinogen 2009; 48:610 - 617
   PubMed Web of Science ®Google Scholar
• Li C, Iida M, Dunn EF, Ghia AJ, Wheeler DL. Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene 2009; 28:3801 - 3813
   PubMed Web of Science ®Google Scholar
• Lin SY, Makino K, Xia WY, Matin A, Wen Y, Kwong KY, et al. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol 2001; 3:802 - 808
   PubMed Web of Science ®Google Scholar
• Li C, Iida M, Dunn EF, Ghia AJ, Wheeler DL. Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene 2009; 28:3801 - 3813
   PubMed Web of Science ®Google Scholar
• Bandyopadhyay D, Mandal M, Adam L, Mendelsohn J, Kumar R. Physical interaction between epidermal growth factor receptor and DNA-dependent protein kinase in mammalian cells. J Biol Chem 1998; 273:1568 - 1573
   PubMed Web of Science ®Google Scholar
• Wheeler DL, Iida M, Kruser TJ, Nechrebecki MM, Dunn EF, Armstrong EA, et al. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab. Cancer Biol Ther 2009; 8:696 - 703
   PubMed Web of Science ®Google Scholar
• Nevo J, Mattila E, Pellinen T, Yamamoto DL, Sara H, Iljin K, et al. Mammary-derived growth inhibitor alters traffic of EGFR and induces a novel form of cetuximab resistance. Clin Cancer Res 2009; 15:6570 - 6581
   PubMed Web of Science ®Google Scholar
• Huynh HT, Larsson C, Narod S, Pollak M. Tumor suppressor activity of the gene encoding mammary-derived growth inhibitor. Cancer Res 1995; 55:2225 - 2231
   PubMed Web of Science ®Google Scholar
• Huynh H, Alpert L, Pollak M. Silencing of the mammary-derived growth inhibitor (MDGI) gene in breast neoplasms is associated with epigenetic changes. Cancer Res 1996; 56:4865 - 4870
   PubMed Web of Science ®Google Scholar
• Specht B, Bartetzko N, Hohoff C, Kuhl H, Franke R, Borchers T, et al. Mammary derived growth inhibitor is not a distinct protein but a mix of heart-type and adipocyte-type fatty acid-binding protein. J Biol Chem 1996; 271:19943 - 19949
   PubMed Web of Science ®Google Scholar
• Spener F, Unterberg C, Borchers T, Grosse R. Characteristics of fatty acid-binding proteins and their relation to mammary-derived growth inhibitor. Mol Cell Biochem 1990; 98:57 - 68
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100:57 - 70
   PubMed Web of Science ®Google Scholar
• Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 2005; 17:548 - 58
   PubMed Web of Science ®Google Scholar
• Thompson EW, Newgreen DF. Carcinoma invasion and metastasis: A role for epithelial-mesenchymal transition?. Cancer Res 2005; 65:5991 - 5995
   PubMed Web of Science ®Google Scholar
• Basu D, Nguyen TTK, Montone KT, Zhang G, Wang LP, Diehl JA, et al. Evidence for mesenchymal-like sub-populations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity. Oncogene 2010; 29:4170 - 4182
   PubMed Web of Science ®Google Scholar
• Strauss R, Sova P, Liu Y, Li ZY, Tuve S, Pritchard D, et al. Epithelial phenotype confers resistance of ovarian cancer cells to oncolytic denoviruses. Cancer Res 2009; 69:5115 - 5125
   PubMed Web of Science ®Google Scholar
• Troussard AA, Mawji NM, Ong C, Mui A, St Arnaud R, Dedhar S. Conditional knock-out of integrin-linked kinase demonstrates an essential role in protein kinase B/Akt activation. J Biol Chem 2003; 278:22374 - 22378
   PubMed Web of Science ®Google Scholar
• Fuchs BC, Fujii T, Dorfman JD, Goodwin JM, Zhu AX, Lanuti M, et al. Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells. Cancer Res 2008; 68:2391 - 2399
   PubMed Web of Science ®Google Scholar
• Kim SM, Kim JS, Kim JH, Yun CO, Kim EM, Kim HK, et al. Acquired resistance to cetuximab is mediated by increased PTEN instability and leads cross-resistance to gefitinib in HCC827 NSCLC cells. Cancer Lett 2010; 296:150 - 159
   PubMed Web of Science ®Google Scholar
• Normanno N, Tejpar S, Morgillo F, De Luca A, Van Cutsem E, Ciardiello F. Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat Rev Clin Oncol 2009; 6:519 - 527
   PubMed Web of Science ®Google Scholar
• De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 2008; 19:508 - 15
   PubMed Web of Science ®Google Scholar
• Bardelli A, Siena S. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 2010; 28:1254 - 1261
   PubMed Web of Science ®Google Scholar
• Dunn EF, Iida M, Myers RA, Campbell DA, Hintz KA, Armstrong EA, et al. Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab. Oncogene 2010; In press
   Web of Science ®Google Scholar
• Hatakeyama H, Cheng HX, Wirth P, Counsell A, Marcrom SR, Wood CB, et al. Regulation of heparin-binding EGF-like growth factor by miR-212 and acquired cetuximab-resistance in head and neck squamous cell carcinoma. PLoS One 2010; 5:e12702
   PubMed Web of Science ®Google Scholar