Drug Resistance Updates
Volume 14, Issue 6 , Pages 260-279 , December 2011

Protein-intrinsic and signaling network-based sources of resistance to EGFR- and ErbB family-targeted therapies in head and neck cancer

  • Ranee Mehra

      Affiliations

    • Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    • Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    • ,
  • Ilya G. Serebriiskii

      Affiliations

    • Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    • ,
  • Roland L. Dunbrack Jr.

      Affiliations

    • Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    • ,
  • Matthew K. Robinson

      Affiliations

    • Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    • ,
  • Barbara Burtness

      Affiliations

    • Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    • Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    • ,
  • Erica A. Golemis

      Affiliations

    • Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    • Corresponding Author InformationCorresponding author at: Fox Chase Cancer Center, W406, 333 Cottman Ave., Philadelphia, PA 19111, USA. Tel.: +1 215 728 2860; fax: +1 215 728 3616.

Received 30 July 2011 ,Revised 16 August 2011 ,Accepted 17 August 2011.

References 

  1. Abidoye OO, Cohen EE, Wong SJ, et al. Phase II study of lapatinib (GW572016) in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). J. Clin. Oncol. (ASCO Ann. Meet. Proc., Part 1). 2006;24(18S):5568
  2. Adams GP, Schier R, McCall , et al. High affinity restricts the localization and tumor penetration of single-chain fv antibody molecules. Cancer Res. 2001;61:4750–4755
  3. Agarwal S, Zerillo C, Kolmakova J, et al. Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells. Br. J. Cancer. 2009;100:941–949
  4. Agrawal N, Frederick MJ, Pickering CR, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011;
  5. Ahsan A, Hiniker SM, Ramanand SG, et al. Role of epidermal growth factor receptor degradation in cisplatin-induced cytotoxicity in head and neck cancer. Cancer Res. 2010;70:2862–2869
  6. Alessi DR, James SR, Downes CP, et al. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr. Biol. 1997;7:261–269
  7. Allen GW, Saba C, Armstrong EA, et al. Insulin-like growth factor-I receptor signaling blockade combined with radiation. Cancer Res. 2007;67:1155–1162
  8. Ammer AG, Kelley LC, Hayes KE, et al. Saracatinib impairs head and neck squamous cell carcinoma invasion by disrupting invadopodia function. J. Cancer Sci. Ther. 2009;1:52–61
  9. Anderson JA, Irish JC, McLachlin CM, Ngan BY. H-ras oncogene mutation and human papillomavirus infection in oral carcinomas. Arch. Otolaryngol. Head Neck Surg. 1994;120:755–760
  10. Ang KK, Berkey BA, Tu X, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002;62:7350–7356
  11. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. New Engl. J. Med. 2010;363(1):24–35
  12. Ang, K.K., Zhang, Q.E., Rosenthal, D.I., et al., 2011. A randomized phase III trial (RTOG 0522) of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III-IV head and neck squamous cell carcinomas (HNC). J. Clin. Oncol. 29 (Suppl.), abstract # 5500.
  13. Anido J, Saez-Borderias A, Gonzalez-Junca A, et al. TGF-beta receptor inhibitors target the CD44(high)/Id1(high) glioma-initiating cell population in human glioblastoma. Cancer Cell. 2010;18:655–668
  14. Arany I, Chen SH, Megyesi JK, et al. Differentiation-dependent expression of signal transducers and activators of transcription (STATs) might modify responses to growth factors in the cancers of the head and neck. Cancer Lett. 2003;199:83–89
  15. Argiris A, Ghebremichael M, Gilbert J, Burtness B, Forastiere AA. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic squamous cell carcinoma of the head and neck: a trial of the ECOG. J. Clin. Oncol. 2009;27(15S):6011;abstract #
  16. Aroian RV, Koga M, Mendel JE, Ohshima Y, Sternberg PW. The let-23 gene necessary for Caenorhabditis Elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily. Nature. 1990;348:693–699
  17. Asiedu MK, Ingle JN, Behrens MD, Radisky DC, Knutson KL. TGF{beta}/TNF{alpha}-mediated epithelial-mesenchymal transition generates breast cancer stem cells with a claudin-low phenotype. Cancer Res. 2011;71:4707–4719
  18. Astsaturov I, Ratushny V, Sukhanova A, et al. Synthetic lethal screen of an EGFR-centered network to improve targeted therapies. Sci. Sign. 2010;3:ra67
  19. Babu KG, Viswanath L, Reddy BK, et al. An open-label, randomized, study of h-R3mAb (nimotuzumab) in patients with advanced (stage III or IVa) squamous cell carcinoma of head and neck: four-year survival results from a phase IIb study. J. Clin. Oncol. 2010;28(15S):abstract # 5530
  20. Balaban N, Moni J, Shannon M, et al. The effect of ionizing radiation on signal transduction: antibodies to EGF receptor sensitize A431 cells to radiation. Biochim. Biophys. Acta. 1996;1314:147–156
  21. Barabasi AL, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat. Rev. Genet. 2011;12:56–68
  22. Bargou R, Leo E, Zugmaier G, et al. Tumor regression in cancer patients by very low doses of a T-cell-engaging antibody. Science. 2008;321:974–977
  23. Barnes CJ, Ohshiro K, Rayala SK, El-Naggar AK, Kumar R. Insulin-like growth factor receptor as a therapeutic target in head and neck cancer. Clin. Cancer Res. 2007;13:4291–4299
  24. Basavaraj C, Sierra P, Shivu J, Melarkode R, Montero E, Nair P. Nimotuzumab with chemoradiation confers a survival advantage in treatment-naive head and neck tumors overexpressing EGFR. Cancer Biol. Ther. 2010;10:673–681
  25. Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat. Rev. Cancer. 2009;9:463–475
  26. Baselga J, Trigo JM, Bourhis J. Phase II mulitcenter study of the antiepidermal growth factor receptor monoclonal antibody cetuimab in combiantion 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
  27. Begum S, Westra WH. Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am. J. Surg. Pathol. 2008;32:1044–1050
  28. Benedettini E, Sholl LM, Peyton M, et al. Met activation in non-small cell lung cancer is associated with de novo resistance to EGFR inhibitors and the development of brain metastasis. Am. J. Pathol. 2010;177:415–423
  29. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. New Engl. J. Med. 2006;354:567–578
  30. Bosco R, Melloni E, Celeghini C, Rimondi E, Vaccarezza M, Zauli G. Fine tuning of protein kinase C (PKC) isoforms in cancer: shortening the distance from the laboratory to the bedside. MiniRev. Med. Chem. 2011;11:185–199
  31. Bostrom J, Yu S-F, Kan D, et al. Variants of the antibody Herpectin that interact with HER2 and VEGF at the antigen binding site. Science. 2009;323:1610–1614
  32. Brand TM, Iida M, Wheeler DL. Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Cancer Biol. Ther. 2011;11:777–792
  33. Brennan JA, Boyle JO, Koch WM, et al. Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcinoma of the head and neck. New Engl. J. Med. 1995;332:712–717
  34. Brooks HD, Glisson BS, Bekele BN, et al. Phase 2 study of dasatinib in the treatment of head and neck squamous cell carcinoma. Cancer. 2011;117:2112–2119
  35. Brusevold IJ, Soland TM, Khuu C, Christoffersen T, Bryne M. Nuclear and cytoplasmic expression of Met in oral squamous cell carcinoma and in an organotypic oral cancer model. Eur. J. Oral Sci. 2010;118:342–349
  36. Buck E, Eyzaguirre A, Rosenfeld-Franklin M, et al. Feedback mechanisms promote cooperativity for small molecule inhibitors of epidermal and insulin-like growth factor receptors. Cancer Res. 2008;68:8322–8332
  37. Burtness B, Goldwasser MA, Flood W. Phase II 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
  38. Cabodi S, Di Stefano P, Leal Mdel P, et al. Integrins and signal transduction. Adv. Exp. Med. Biol. 2010;674:43–54
  39. Cai X, Zhai HX, Wang J, et al. Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanam ide (CUDc-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer. J. Med. Chem. 2010;53:2000–2009
  40. Cemeus C, Zhao TT, Barrett GM, Lorimer IA, Dimitroulakos J. Lovastatin enhances gefitinib activity in glioblastoma cells irrespective of EGFRvIII and PTEN status. J. Neurooncol. 2008;90:9–17
  41. Chakravarti A, Loeffler JS, Dyson NJ. 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;62:200–207
  42. Chames P, Baty D. Bispecific antibodies for cancer therapy: the light at the end of the tunnel?. mAbs. 2009;1:539–547
  43. Chaturvedi A, Engels E, Pfeiffer R, et al. Human papillomavirus (HPV) and rising oropharyngeal cancer incidence and survival in the United States. J. Clin. Oncol. 2011;29(Suppl.):abstract # 5529
  44. Chau NG, Perez-Ordonez B, Zhang K, et al. The association between EGFR variant III, HPV, p16, c-MET, EGFR gene copy number and response to EGFR inhibitors in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Head Neck Oncol. 2011;3:11
  45. Chen D, Nirodi C. The epidermal growth factor receptor: a role in repair of radiation-induced DNA damage. Clin. Cancer Res. 2007;13:6555–6560
  46. Clark AS, West KA, Blumberg PM, Dennis PA. Altered protein kinase C (PKC) isoforms in non-small cell lung cancer cells: PKCdelta promotes cellular survival and chemotherapeutic resistance. Cancer Res. 2003;63:780–786
  47. Cohen EE, Rosen F, Stadler WM, et al. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J. Clin. Oncol. 2003;21:1980–1987
  48. Cohen S, Carpenter G, King L. Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity. J. Biol. Chem. 1980;255:4834–4842
  49. Comoglio PM, Giordano S, Trusolino L. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat. Rev. Drug Discov. 2008;7:504–516
  50. Connolly, E.C., Akhurst, R.J., 2011. The complexities of TGF-beta action during mammary and squamous cell carcinogenesis. Curr. Pharm. Biotechnol. (Epub ahead of print).
  51. Connolly EC, Saunier EF, Quigley D, et al. Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long-term TbetaRI/II kinase inhibition with LY2109761. Cancer Res. 2011;71:2339–2349
  52. Contessa JN, Bhojani MS, Freeze HH, Rehemtulla A, Lawrence TS. Inhibition of N-linked glycosylation disrupts receptor tyrosine kinase signaling in tumor cells. Cancer Res. 2008;68:3803–3809
  53. Coppola D, Ferber A, Miura M, et al. A functional insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the epidermal growth factor receptor. Mol. Cell. Biol. 1994;14:4588–4595
  54. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N. Engl. J. Med. 2007;356:1944–1956
  55. Dassonville O, Formento JL, Francoual M, et al. Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer. J. Clin. Oncol. 1993;11:1873–1878
  56. Davis JH, Aperlo C, Li Y, et al. SEEDbodies: fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies. Protein Eng. Des. Sel. 2010;23:195–202
  57. Denlinger CS, Beeram M, Tolcher AW, et al. A phase I/II and pharmacologic study of MM-111 in patients with advanced, refractory HER2-positive (HER2+) cancers. J. Clin. Oncol. 2010;28(15S):TPS169
  58. Dong J, Sereno A, Aivazian D, et al. A stable IgG-like bispecific antibody targeting the epidermal growth factor receptor and the type I insulin-like growth factor receptor demonstrates superior anti-tumor activity. mAbs. 2011;3:273–288
  59. Eder JP, Shapiro GI, Appleman LJ, et al. A phase I study of foretinib, a multi-targeted inhibitor of c-Met and vascular endothelial growth factor receptor 2. Clin. Cancer Res. 2010;16:3507–3516
  60. Edgar KA, Wallin JJ, Berry M, et al. Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors. Cancer Res. 2010;70:1164–1172
  61. Egloff AM, Grandis JR. Improving response rates to EGFR-targeted therapies for head and neck squamous cell carcinoma: candidate predictive biomarkers and combination treatment with Src Inhibitors. J. Oncol. 2009;2009:896407
  62. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039–1043
  63. Faber AC, Li D, Song Y, et al. Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition. Proc. Natl. Acad. Sci. U.S.A. 2009;106:19503–19508
  64. Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J. Natl. Cancer Inst. 2008;100:261–269
  65. Feinmesser RL, Wicks SJ, Taverner CJ, Chantry A. Ca2+/calmodulin-dependent kinase II phosphorylates the epidermal growth factor receptor on multiple sites in the cytoplasmic tail and serine 744 within the kinase domain to regulate signal generation. J. Biol. Chem. 1999;274:16168–16173
  66. Fernandes H, Cohen S, Bishayee S. Glycosylation-induced conformational modification positively regulates receptor-receptor association: a study with an aberrant epidermal growth factor receptor (EGFRvIII/DeltaEGFR) expressed in cancer cells. J. Biol. Chem. 2001;276:5375–5383
  67. Fiedler WM, Ritter B, Seggewiss R, et al. Phase I safety and pharmacology study of the EPCAM/CD3-bispecific antibody MT110 in patients with metastatic colorectal, gastric, or lung cancer. J. Clin. Oncol. 2010;28(15S):abstract # 2573
  68. Forbes, S.A., Bhamra, G., Bamford, S., et al., 2008. The catalogue of somatic mutations in cancer (COSMIC). Curr. Protoc. Hum. Genet., Chapter 10. Unit 10 11.
  69. Friedmann B, Caplin M, Hartley JA, Hochhauser D. Modulation of DNA repair in vitro after treatment with chemotherapeutic agents by the epidermal growth factor receptor inhibitor gefitinib (ZD1839). Clin. Cancer Res. 2004;10:6476–6486
  70. Friend SH, Ideker T. Point: Are we prepared for the future doctor visit?. Nat. Biotechnol. 2011;29:215–218
  71. Fury MG, Baxi S, Shen R, et al. Phase II study of saracatinib (AZD0530) for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Anticancer Res. 2011;31:249–253
  72. Ge L, Baskic D, Basse P, et al. Sheddase activity of tumor necrosis factor-alpha converting enzyme is increased and prognostically valuable in head and neck cancer. Cancer Epidemiol. Biomarkers Prev. 2009;18:2913–2922
  73. Ghadjar P, Blank-Liss W, Simcock M, et al. MET Y1253D-activating point mutation and development of distant metastasis in advanced head and neck cancers. Clin. Exp. Metast. 2009;26:809–815
  74. Gillison ML, D'Souza G, Westra W, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J. Natl. Cancer Inst. 2008;100:407–420
  75. Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J. Natl. Cancer Inst. 2000;92:709–720
  76. Giri DK, Ali-Seyed M, Li LY, et al. Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor. Mol. Cell. Biol. 2005;25:11005–11018
  77. Goh LK, Huang F, Kim W, Gygi S, Sorkin A. Multiple mechanisms collectively regulate clathrin-mediated endocytosis of the epidermal growth factor receptor. J. Cell. Biol. 2010;189:871–883
  78. Goldstein NI, Prewett M, Zuklys K, Rockwell P, Mendelsohn J. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor ina human tumor xenograft model. Clin. Cancer Res. 1995;1:1311–1318
  79. Gonzalez E, McGraw TE. The Akt kinases: isoform specificity in metabolism and cancer. Cell Cycle. 2009;8:2502–2508
  80. Gordon MS, Sweeney CS, Mendelson DS, et al. Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors. Clin. Cancer Res. 2010;16:699–710
  81. Gualberto A, Hixon ML, Karp DD, et al. Pre-treatment levels of circulating free IGF-1 identify NSCLC patients who derive clinical benefit from figitumumab. Br. J. Cancer. 2011;104:68–74
  82. Guix M, Faber AC, Wang SE, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J. Clin. Invest. 2008;118:2609–2619
  83. Gunasekaran K, Pentony M, Shen M, et al. Enhancing antibody Fc heterodimer formation through electrostatic steering effects: applications to bispecific molecules and monovalent IgG. J. Biol. Chem. 2010;285:19637–19646
  84. Guo A, Villen J, Kornhauser J, et al. Signaling networks assembled by oncogenic EGFR and c-Met. Proc. Natl. Acad. Sci. U.S.A. 2008;105:692–697
  85. Hama T, Yuza Y, Saito Y, et al. Prognostic significance of epidermal growth factor receptor phosphorylation and mutation in head and neck squamous cell carcinoma. Oncologist. 2009;14:900–908
  86. Han M, Aroian RV, Sternberg PW. The let-60 locus controls the switch between vulval and nonvulval cell fates in Caenorhabditis elegans. Genetics. 1990;126:899–913
  87. Harari PM, Huang SM. Head and neck cancer as a clinical model for molecular targeting of therapy: combining EGFR blockade with radiation. Int. J. Rad. Oncol. Biol. Phys. 2001;49:427–433
  88. Harrington KJ, Berrier A, Robinson M, et al. Phase II study of oral lapatinib, a dual-tyrosine kinase inhibitor, combined with chemoradiotherapy (CRT) in patients (pts) with locally advanced, unresected squamous cell carcinoma of the head and neck (SCCHN). J. Clin. Oncol. 2010;28(15S):abstract # 5505
  89. Harrington KJ, El-Hariry IA, Holford CS, et al. Phase I study of lapatinib in combination with chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck. J. Clin. Oncol. 2009;27:1100–1107
  90. Hatakeyama H, Cheng H, Wirth P, 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
  91. Herbst RS, Arquette M, Shin DM. 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;23:5568–5577
  92. Hickinson DM, Marshall GB, Beran GJ, et al. Identification of biomarkers in human head and neck tumor cell lines that predict for in vitro sensitivity to gefitinib. Clin. Transl. Sci. 2009;2:183–192
  93. Higginbotham JN, Demory Beckler M, Gephart JD, et al. Amphiregulin exosomes increase cancer cell invasion. Curr. Biol. 2011;21:779–786
  94. Hsu JM, Chen CT, Chou CK, et al. Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat. Cell Biol. 2011;13:174–181
  95. Hsu SC, Hung MC. Characterization of a novel tripartite nuclear localization sequence in the EGFR family. J. Biol. Chem. 2007;282:10432–10440
  96. Huang F, Greer A, Hurlburt W, et al. The mechanisms of differential sensitivity to an insulin-like growth factor-1 receptor inhibitor (BMS-536924) and rationale for combining with EGFR/HER2 inhibitors. Cancer Res. 2009;69:161–170
  97. 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
  98. Hung LY, Tseng JT, Lee YC, 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
  99. Inman GJ. Switching TGFbeta from a tumor suppressor to a tumor promoter. Curr. Opin. Genet. Dev. 2011;21:93–99
  100. Jager M, Schoberth A, Ruf P, Hess J, Lindhofer H. The trifunctional antibody ertumaxomab destroys tumor cells that express low levels of human epidermal growth factor receptor 2. Cancer Res. 2009;69:4270–4276
  101. Jaramillo ML, Leon Z, Grothe S, et al. Effect of the anti-receptor ligand-blocking 225 monoclonal antibody on EGF receptor endocytosis and sorting. Exp. Cell Res. 2006;312:2778–2790
  102. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J. Clin. 2007;57:43–66
  103. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J. Clin. 2010;60:277–300
  104. Jhawer M, Goel S, Wilson AJ, et al. PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res. 2008;68:1953–1961
  105. Johns TG, Mellman I, Cartwright GA, et al. The antitumor monoclonal antibody 806 recognizes a high-mannose form of the EGF receptor that reaches the cell surface when cells over-express the receptor. FASEB J. 2005;19:780–782
  106. Johnson FM, Saigal B, Talpaz M, Donato NJ. Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung cancer cells. Clin. Cancer Res. 2005;11:6924–6932
  107. Jutten B, Dubois L, Li Y, et al. Binding of cetuximab to the EGFRvIII deletion mutant and its biological consequences in malignant glioma cells. Radiother. Oncol. 2009;92:393–398
  108. Kancha RK, von Bubnoff N, Peschel C, Duyster J. Functional analysis of epidermal growth factor receptor (EGFR) mutations and potential implications for EGFR targeted therapy. Clin. Cancer Res. 2009;15:460–467
  109. Khambata-Ford S, Garrett CR, Meropol NJ, 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
  110. Kim CH, Koh YW, Han JH, et al. c-Met expression as an indicator of survival outcome in patients with oral tongue carcinoma. Head Neck. 2010;32:1655–1664
  111. Kiyota A, Shintani S, Mihara M, et al. Anti-epidermal growth factor receptor monoclonal antibody 225 upregulates p27(KIP1) and p15(INK4B) and induces G1 arrest in oral squamous carcinoma cell lines. Oncology. 2002;63:92–98
  112. Knowles LM, Stabile LP, Egloff AM, et al. HGF and c-Met participate in paracrine tumorigenic pathways in head and neck squamous cell cancer. Clin. Cancer Res. 2009;15:3740–3750
  113. Ko SY, Lin SC, Wong YK, et al. Increase of disintergin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma. Cancer Lett. 2007;245:33–43
  114. Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 2005;352:786–792
  115. Kohane IS, Margulies DM. Counterpoint: do not opine before it's time. Nat. Biotechnol. 2011;29:218–219
  116. Kondo N, Tsukuda M, Ishiguro Y, et al. Antitumor effects of lapatinib (GW572016), a dual inhibitor of EGFR and HER-2, in combination with cisplatin or paclitaxel on head and neck squamous cell carcinoma. Oncol. Rep. 2010;23:957–963
  117. Kong CS, Narasimhan B, Cao H, et al. The relationship between human papillomavirus status and other molecular prognostic markers in head and neck squamous cell carcinomas. Int. J. Rad. Oncol. Biol. Phys. 2009;74:553–561
  118. Kornfeld JW, Meder S, Wohlberg M, et al. Overexpression of TACE and TIMP3 mRNA in head and neck cancer: association with tumour development and progression. Br. J. Cancer. 2011;104:138–145
  119. Korpal M, Kang Y. Targeting the transforming growth factor-beta signalling pathway in metastatic cancer. Eur. J. Cancer. 2010;46:1232–1240
  120. Kruser TJ, Armstrong EA, Ghia AJ, et al. Augmentation of radiation response by panitumumab in models of upper aerodigestive tract cancer. Int. J. Rad. Oncol. Biol. Phys. 2008;72:534–542
  121. Kudo Y, Tsunematsu T, Takata T. Oncogenic role of RUNX3 in head and neck cancer. J. Cell. Biochem. 2011;112:387–393
  122. Kuenen B, Witteveen PO, Ruijter R, et al. A phase I pharmacologic study of necitumumab, a fully human IgG1 monoclonal antibody directed against EGFR in patients with advanced solid malignancies. Clin. Cancer Res. 2010;16:1915–1923
  123. Kurai J, Chikumi H, Hashimoto K. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin. Cancer Res. 2007;13:1552–1561
  124. Kyula JN, Van Schaeybroeck S, Doherty J, et al. Chemotherapy-induced activation of ADAM-17: a novel mechanism of drug resistance in colorectal cancer. Clin. Cancer Res. 2010;16:3378–3389
  125. Lai SY, Johnson FM. Defining the role of the JAK-STAT pathway in head and neck and thoracic malignancies: implications for future therapeutic approaches. Drug Resist. Updates. 2010;13:67–78
  126. Lane MD, Ronnett G, Slieker LJ, Kohanski RA, Olson TL. Post-translational processing and activation of insulin and EGF proreceptors. Biochimie. 1985;67:1069–1080
  127. Laurent-Puig P, Cayre A, Manceau G, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J. Clin. Oncol. 2009;27:5924–5930
  128. Lax I, Fischer R, Ng C, et al. Noncontiguous regions in the extracellular domain of EGF receptor define ligand-binding specificity. Cell Regul. 1991;2:337–345
  129. Lee JW, Soung YH, Kim SY, et al. Somatic mutations of EGFR gene in squamous cell carcinoma of the head and neck. Clin. Cancer Res. 2005;11:2879–2882
  130. Leeman RJ, Lui VW, Grandis JR. STAT3 as a therapeutic target in head and neck cancer. Expert Opin. Biol. Ther. 2006;6:231–241
  131. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat. Rev. Cancer. 2011;11:9–22
  132. Li C, Iida M, Dunn EF, Ghia AJ, Wheeler DL. Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene. 2009;28:3801–3813
  133. Li S, Kussie P, Ferguson KM. Structural basis for EGF receptor inhibition by the therapeutic antibody IMC-11F8. Structure. 2008;16:216–227
  134. Li S, Schmitz K, Jeffrey P, et al. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell. 2005;7:301–311
  135. 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
  136. Liao HJ, Carpenter G. Cetuximab/C225-induced intracellular trafficking of epidermal growth factor receptor. Cancer Res. 2009;69:6179–6183
  137. Ling YH, Li T, Perez-Soler R, Haigentz M. Activation of ER stress and inhibition of EGFR N-glycosylation by tunicamycin enhances susceptibility of human non-small cell lung cancer cells to erlotinib. Cancer Chemother. Pharmacol. 2009;64:539–548
  138. Liska D, Chen CT, Bachleitner-Hofmann T, Christensen JG, Weiser MR. HGF rescues colorectal cancer cells from EGFR inhibition via MET activation. Clin. Cancer Res. 2011;17:472–482
  139. Lo HW. Nuclear mode of the EGFR signaling network: biology, prognostic value, and therapeutic implications. Discov. Med. 2010;10:44–51
  140. Lo HW, Hsu SC, Ali-Seyed M, et al. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell. 2005;7:575–589
  141. Loeffler-Ragg J, Witsch-Baumgartner M, Tzankov A, et al. Low incidence of mutations in EGFR kinase domain in Caucasian patients with head and neck squamous cell carcinoma. Eur. J. Cancer. 2006;42:109–111
  142. Lonberg N. Fully human antibodies from transgenic mouse and phage display platforms. Curr. Opin. Immunol. 2008;20:450–459
  143. Lopez-Albaitero A, Ferris R. Immune activation by epidermal growth factor receptor specific monoclonal antibody therapy for head and neck cancer. Arch. Otolaryngol. Head Neck Surg. 2007;133:1277–1281
  144. Lopez-Albaitero A, Lee SC, Morgan S, et al. Role of polymorphic Fc gamma receptor IIIa and EGFR expression level in cetuximab mediated, NK cell dependent in vitro cytotoxicity of head and neck squamous cell carcinoma cells. Cancer Immunol. Immunother. 2009;58:1855–1864
  145. LoPiccolo J, Blumenthal GM, Bernstein WB, Dennis PA. Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist. Updates. 2008;11:32–50
  146. Lowenstein EJ, Daly RJ, Batzer AG, et al. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992;70:431–442
  147. Lu D, Zhang H, Koo H, et al. A fully human recombinant IgG-like bispecific antibody to both the epidermal growth factor receptor and the insulin-like growth factor receptor for enhanced antitumor activity. J. Biol. Chem. 2005;280:19665–19672
  148. Ludovini V, Bianconi F, Pistola L, et al. Phosphoinositide-3-kinase catalytic alpha and KRAS mutations are important predictors of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer. J. Thorac. Oncol. 2011;6:707–715
  149. Machiels JP, Schmitz S. Molecular-targeted therapy of head and neck squamous cell carcinoma: beyond cetuximab-based therapy. Curr. Opin. Oncol. 2011;23:241–248
  150. Machiels JP, Subramanian S, Ruzsa A, et al. Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial. Lancet Oncol. 2011;12:333–343
  151. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–715
  152. Masuda M, Suzui M, Yasumatu R, et al. Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res. 2002;62:3351–3355
  153. Masui H, Kawamoto T, Sato JD, et al. Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res. 1984;44:1002–1007
  154. Merchant AM, Zhu Z, Yuan JQ, et al. An efficient route to human bispecific IgG. Nat. Biotechnol. 1998;16:677–681
  155. Messa C, Russo F, Caruso MG, Di Leo A. EGF, TGF-alpha, and EGF-R in human colorectal adenocarcinoma. Acta Oncol. (Stockholm). 1998;37:285–289
  156. Milas L, Mason K, Hunter N, et al. In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin. Cancer Res. 2000;6:701–708
  157. Minkovsky N, Berezov A. BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors. Curr. Opin. Invest. Drugs. 2008;9:1336–1346
  158. Murray S, Bobos M, Angouridakis N, et al. Screening for EGFR mutations in patients with head and neck cancer treated with gefitinib on a compassionate-use program: a Hellenic Cooperative Oncology Group Study. J. Oncol. 2010;2010:709678
  159. Naka K, Hoshii T, Muraguchi T, et al. TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature. 2010;463:676–680
  160. Nozawa H, Howell G, Suzuki S, et al. Combined inhibition of PLC{gamma}-1 and c-Src abrogates epidermal growth factor receptor-mediated head and neck squamous cell carcinoma invasion. Clin. Cancer Res. 2008;14:4336–4344
  161. O-charoenrat P, Rhys-Evans PH, Modjtahedi H, Eccles SA. The role of c-erbB receptors and ligands in head and neck squamous cell carcinoma. Oral Oncol. 2002;38:627–640
  162. O-charoenrat P, Wongkajornsilp A, Rhys-Evans PH, Eccles SA. Signaling pathways required for matrix metalloproteinase-9 induction by betacellulin in head-and-neck squamous carcinoma cells. Int. J. Cancer. 2004;111:174–183
  163. Ogawa A, Takayama Y, Sakai H, et al. Structure of the carboxyl-terminal Src kinase Csk. J. Biol. Chem. 2002;277:14351–14354
  164. Ogiso H, Ishitani R, Nureki O, et al. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains. Cell. 2002;110:775–787
  165. Oh SH, Jin Q, Kim ES, Khuri FR, Lee HY. Insulin-like growth factor-I receptor signaling pathway induces resistance to the apoptotic activities of SCH66336 (lonafarnib) through Akt/mammalian target of rapamycin-mediated increases in survivin expression. Clin. Cancer Res. 2008;14:1581–1589
  166. Oksvold MP, Thien CB, Widerberg J, et al. Serine mutations that abrogate ligand-induced ubiquitination and internalization of the EGF receptor do not affect c-Cbl association with the receptor. Oncogene. 2003;22:8509–8518
  167. Oksvold MP, Thien CB, Widerberg J, et al. UV-radiation-induced internalization of the epidermal growth factor receptor requires distinct serine and tyrosine residues in the cytoplasmic carboxy-terminal domain. Radiat. Res. 2004;161:685–691
  168. Orcutt KD, Ackerman ME, Cieslewicz M, et al. A modular IgG-scFv bispecific antibody topology. Protein Eng. Des. Sel. 2010;23:221–228
  169. Orth JD, Krueger EW, Weller SG, McNiven MA. A novel endocytic mechanism of epidermal growth factor receptor sequestration and internalization. Cancer Res. 2006;66:3603–3610
  170. Pao W, Chmielecki J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat. Rev. Cancer. 2011;10:760–774
  171. Pao W, Miller VA, Politi KA, 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:e73
  172. Park IH, Kim JY, Jung JI, Han JY. Lovastatin overcomes gefitinib resistance in human non-small cell lung cancer cells with K-Ras mutations. Invest. New Drugs. 2010;28:791–799
  173. Pectasides E, Egloff AM, Sasaki C, et al. Nuclear localization of stat-3 in head and neck squamous cell carcinoma is associated with a better prognosis. Clin. Cancer Res. 2010;16:2427–2434
  174. Pedersen MW, Pedersen N, Ottesen LH, Poulsen HS. Differential response to gefitinib of cells expressing normal EGFR and the mutant EGFRvIII. Br. J. Cancer. 2005;93:915–923
  175. Peng Y, Li Y, Gellert LL, et al. Androgen receptor coactivator p44/Mep50 in breast cancer growth and invasion. J. Cell. Mol. Med. 2009;14:2780–2789
  176. Perrone F, Suardi S, Pastore E, et al. Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma. Clin. Cancer Res. 2006;12:6643–6651
  177. Poeta ML, Manola J, Goldwasser MA, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N. Engl. J. Med. 2007;357:2552–2561
  178. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat. Rev. Cancer. 2008;8:915–928
  179. Posner MR, Lorch JH, Goloubeva O, et al. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann. Oncol. 2011;22:1071–1077
  180. Prigent SA, Lemoine NR. The type 1 (EGFR-related) family of growth factor receptors and their ligands. Progr. Growth Factor Res. 1992;4:1–24
  181. Psyrri A, Egleston B, Weinberger P, et al. Correlates and determinants of nuclear epidermal growth factor receptor content in an oropharyngeal cancer tissue microarray. Cancer Epidemiol. Biomarkers Prev. 2008;17:1486–1492
  182. Psyrri A, Yu Z, Weinberger PM, 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
  183. Pugacheva EN, Golemis EA. HEF1-aurora A interactions: points of dialog between the cell cycle and cell attachment signaling networks. Cell Cycle. 2006;5:384–391
  184. Qian F, Engst S, Yamaguchi K, et al. Inhibition of tumor cell growth, invasion and metastasis by EXEL-2880 (GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases. Cancer Res. 2009;69:8009–8016
  185. Quesnelle KM, Boehm AL, Grandis JR. STAT-mediated EGFR signaling in cancer. J. Cell. Biochem. 2007;102:311–319
  186. Ratushny V, Astsaturov I, Burtness BA, Golemis EA, Silverman JS. Targeting EGFR resistance networks in head and neck cancer. Cell Signal. 2009;21:1255–1268
  187. Ratushny V, Pathak HB, Beeharry N, et al. Dual inhibition of SRC and Aurora kinases induces postmitotic attachment defects and cell death. Oncogene. 2011;
  188. Raynaud FI, Eccles SA, Patel S, et al. Biological properties of potent inhibitors of class I phosphatidyl-inositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol. Cancer Ther. 2009;8:1725–1738
  189. Reusch U, Sundaram M, Davol PA, et al. Anti-CD3 x anti-epidermal growth factor receptor bispecific antibody redirects T-cell cytolytic activity to EGFR-positive cancers in vitro and in an animal model. Clin. Cancer Res. 2006;12:183–190
  190. Riesterer O, Yang Q, Raju U, et al. Combination of anti-IGF-1R antibody A12 and ionizing radiation in upper respiratory tract cancers. Int. J. Rad. Oncol. Biol. Phys. 2011;79:1179–1187
  191. Rischin D, Young R, Fisher R, et al. Prognostic significance of HPV and p16 status in patients with oropharyngeal cancer treated on a large international phase III trial. J. Clin. Oncol. 2009;27(15S):abstract # 6004
  192. Rischin D, Young RJ, Fisher R, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J. Clin. Oncol. 2010;28:4142–4148
  193. Roderick HL, Cook SJ. Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival. Nat. Rev. Cancer. 2008;8:361–375
  194. Rosse C, Linch M, Kermorgant S, Cameron AJ, Boeckeler K, Parker PJ. PKC and the control of localized signal dynamics. Nat. Rev. Mol. Cell. Biol. 2010;11:103–112
  195. Rubin Grandis J, Melhem MF, Gooding WE, et al. Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J. Natl. Cancer Inst. 1998;90:824–832
  196. Saftig P, Reiss K. The “A Disintegrin And Metalloproteases” ADAM10 and ADAM17: novel drug targets with therapeutic potential?. Eur. J. Cell Biol. 2011;90:527–535
  197. Sartore-Bianchi A, Di Nicolantonio F, Nichelatti M, et al. Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer. PLoS one. 2009;4:e7287
  198. Sartore-Bianchi A, Martini M, Molinari F, et al. PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res. 2009;69:1851–1857
  199. Schaefer GM. Targeting EGFR and HER3 with a “two-in-one antibody”. Proc. Am. Assoc. Cancer Res. 2010;abstract #DD01-02
  200. Schroeder B, Weller SG, Chen J, Billadeau D, McNiven MA. A Dyn2-CIN85 complex mediates degradative traffic of the EGFR by regulation of late endosomal budding. EMBO J. 2010;29:3039–3053
  201. Schwentner I, Witsch-Baumgartner M, Sprinzl GM, et al. Identification of the rare EGFR mutation pG796S as somatic and germline mutation in white patients with squamous cell carcinoma of the head and neck. Head Neck. 2008;30:1040–1044
  202. Seethala RR, Gooding WE, Handler PN, et al. Immunohistochemical analysis of phosphotyrosine signal transducer and activator of transcription 3 and epidermal growth factor receptor autocrine signaling pathways in head and neck cancers and metastatic lymph nodes. Clin. Cancer Res. 2008;14:1303–1309
  203. Seiwert TY, Jagadeeswaran R, Faoro L, et al. The MET receptor tyrosine kinase is a potential novel therapeutic target for head and neck squamous cell carcinoma. Cancer Res. 2009;69:3021–3031
  204. Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl. Med. 2011;3:75ra26
  205. Sheng ZM, Barrois M, Klijanienko J, et al. Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas. Br. J. Cancer. 1990;62:398–404
  206. Sheridan MT, O’Dwyer T, Seymour CB, Mothersill CE. Potential indicators of radiosensitivity in squamous cell carcinoma of the head and neck. Radiat. Oncol. Invest. 1997;5:180–186
  207. Shigeishi H, Higashikawa K, Hiraoka M, et al. Expression of epiregulin, a novel epidermal growth factor ligand associated with prognosis in human oral squamous cell carcinomas. Oncol. Rep. 2008;19:1557–1564
  208. Sigismund S, Argenzio E, Tosoni D, et al. Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation. Dev. Cell. 2008;15:209–219
  209. Sigismund S, Woelk T, Puri C. Clathrin-independent endocytosis of ubiquitinated cargos. Proc. Natl. Acad. Sci. U.S.A. 2005;102:2760–2765
  210. Slomiany MG, Black LA, Kibbey MM, Day TA, Rosenzweig SA. IGF-1 induced vascular endothelial growth factor secretion in head and neck squamous cell carcinoma. Biochem. Biophys. Res. Commun. 2006;342:851–858
  211. Sok JC, Coppelli FM, Thomas SM, et al. Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin. Cancer Res. 2006;12:5064–5073
  212. Sorkin A, Goh LK. Endocytosis and intracellular trafficking of ErbBs. Exp. Cell Res. 2009;315:683–696
  213. Soulieres D, Senzer NN, Vokes EE, et al. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J. Clin. Oncol. 2004;22:77–85
  214. Stokes A, Joutsa J, Ala-Aho R, et al. Expression profiles and clinical correlations of degradome components in the tumor microenvironment of head and neck squamous cell carcinoma. Clin. Cancer Res. 2010;16:2022–2035
  215. Stransky N, Egloff AM, Tward AD, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;
  216. Tanaka H, Yoshida M, Tanimura H, et al. The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin. Cancer Res. 2011;17:3272–3281
  217. Thomas SM, Coppelli FM, Wells A, et al. Epidermal growth factor receptor-stimulated activation of phospholipase Cgamma-1 promotes invasion of head and neck squamous cell carcinoma. Cancer Res. 2003;63:5629–5635
  218. Tikhmyanova N, Little JL, Golemis EA. CAS proteins in normal and pathological cell growth control. Cell. Mol. Life Sci. 2010;67:1025–1048
  219. Tinhofer I, Klinghammer K, Weichert W, et al. Expression of Amphiregulin and EGFRvIII affect outcome of patients with squamous cell carcinoma of the head and neck (SCCHN) receiving cetuximab-docetaxel treatment. Clin. Cancer Res. 2011;17:5197–5204
  220. Tong J, Taylor P, Peterman SM, Prakash A, Moran MF. Epidermal growth factor receptor phosphorylation sites Ser991 and Tyr998 are implicated in the regulation of receptor endocytosis and phosphorylations at Ser1039 and Thr1041. Mol. Cell. Prot. 2009;8:2131–2144
  221. Toton E, Ignatowicz E, Skrzeczkowska K, Rybczynska M. Protein kinase Cepsilon as a cancer marker and target for anticancer therapy. Pharmacol. Rep. 2011;63:19–29
  222. Turke AB, Zejnullahu K, Wu YL, et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell. 2010;17:77–88
  223. Vakiani E, Solit DB. KRAS and BRAF: drug targets and predictive biomarkers. J. Pathol. 2011;223:219–229
  224. Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J. Clin. Oncol. 2007;25:1658–1664
  225. van der Veeken J, Oliveira S, Schiffelers RM, et al. Crosstalk between epidermal growth factor receptor- and insulin-like growth factor-1 receptor signaling: implications for cancer therapy. Curr. Cancer Drug Targets. 2009;9:748–760
  226. Van Schaeybroeck S, Kyula JN, Fenton A, et al. Oncogenic Kras promotes chemotherapy-induced growth factor shedding via ADAM17. Cancer Res. 2010;71:1071–1080
  227. Vermorken JB, Mesia R, Rivera F. Platinum based chemotherapy plus cetuximab in head and neck cancer. N. Engl. J. Med. 2008;359:1116–1127
  228. Vermorken JB, Trigo J, Hitt R. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/ormetastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J. Clin. Oncol. 2007;25:2171–2177
  229. Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J. Clin. Oncol. 2007;25:2171–2177
  230. Vivanco I, Palaskas N, Tran C, et al. Identification of the JNK signaling pathway as a functional target of the tumor suppressor PTEN. Cancer Cell. 2007;11:555–569
  231. Wakasaki T, Masuda M, Niiro H, et al. A critical role of c-Cbl-interacting protein of 85 kDa in the development and progression of head and neck squamous cell carcinomas through the ras-ERK pathway. Neoplasia. 2010;12:789–796
  232. Wang X, Schneider A. HIF-2alpha-mediated activation of the epidermal growth factor receptor potentiates head and neck cancer cell migration in response to hypoxia. Carcinogenesis. 2010;31:1202–1210
  233. Wanner G, Mayer C, Kehlbach R, Rodemann H, Dittmann K. Activation of protein kinase C epsilon stimulates DNA repair via epidermal growth factor nuclear accumulation. Radiother. Oncol. 2008;86:383–390
  234. Wee S, Wiederschain D, Maira SM, et al. PTEN-deficient cancers depend on PIK3CB. Proc. Natl. Acad. Sci. U.S.A. 2008;105:13057–13062
  235. Weinberger PM, Yu Z, Haffty BG, et al. Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis. J. Clin. Oncol. 2006;24:736–747
  236. Westra WH, Taube JM, Poeta ML, et al. Inverse relationship between human papillomavirus-16 infection and disruptive p53 gene mutations in squamous cell carcinoma of the head and neck. Clin. Cancer Res. 2008;14:366–369
  237. Wheeler DL, Dunn EF, Harari PM. Understanding resistance to EGFR inhibitors-impact on future treatment strategies. Nat. Rev. Clin. Oncol. 2010;7:493–507
  238. Wheeler DL, Huang S, Kruser TJ, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members. Oncogene. 2008;27:3944–3956
  239. Wheeler DL, Iida M, Dunn EF. The role of Src in solid tumors. Oncologist. 2009;14:667–678
  240. Wheeler DL, Iida M, Kruser TJ, et al. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab. Cancer Biol. Ther. 2009;8:696–703
  241. White RA, Malkoski SP, Wang XJ. TGFbeta signaling in head and neck squamous cell carcinoma. Oncogene. 2010;29:5437–5446
  242. Whitson KB, Whitson SR, Red-Brewer ML, et al. Functional effects of glycosylation at Asn-579 of the epidermal growth factor receptor. Biochemistry. 2005;44:14920–14931
  243. Wirth LJ, Allen AM, Posner MR, et al. Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck. Ann. Oncol. 2010;21:342–347
  244. Wirth LJ, Tishler RB, Haddad RI, et al. Phase I study of panitumumab, chemotherapy and intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC): early results. J. Clin. Oncol. (ASCO Ann. Meet. Proc. Part 1). 2007;25(18S):abstract # 6083
  245. Won YW, Han JY, Lee GK, et al. Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations. J. Clin. Pathol. 2011;
  246. Wu C, Ying H, Bose S, et al. Molecular construction and optimization of anti-human IL-1alpha/beta dual variable domain immunoglobulin (DVD-Ig) molecules. mAbs. 2009;1:339–347
  247. Wu X, Zhao H, Do KA, et al. Serum levels of insulin growth factor (IGF-I) and IGF-binding protein predict risk of second primary tumors in patients with head and neck cancer. Clin. Cancer Res. 2004;10:3988–3995
  248. Xiao H, Zhang Q, Shen J, Bindokas V, Xing HR. Pharmacologic inactivation of kinase suppressor of Ras1 sensitizes epidermal growth factor receptor and oncogenic Ras-dependent tumors to ionizing radiation treatment. Mol. Cancer Ther. 2010;9:2724–2736
  249. Xie LQ, Bian LJ, Li Z, Li Y, Liang YJ. Co-elevated expression of hepatocyte growth factor and Interleukin-8 contributes to poor prognosis of patients with primary nasopharyngeal carcinoma. Oncol. Rep. 2010;23:141–150
  250. Xu L, Nilsson MB, Saintigny P, et al. Epidermal growth factor receptor regulates MET levels and invasiveness through hypoxia-inducible factor-1alpha in non-small cell lung cancer cells. Oncogene. 2010;29:2616–2627
  251. Yacoub A, McKinstry R, Hinman D, Chung T, Dent P, Hagan MP. Epidermal growth factor and ionizing radiation up-regulate the DNA repair genes XRCC1 and ERCC1 in DU145 and LNCaP prostate carcinoma through MAPK signaling. Radiat. Res. 2003;159:439–452
  252. Yang S, Qu S, Perez-Tores M, et al. Association with HSP90 inhibits Cbl-mediated down-regulation of mutant epidermal growth factor receptors. Cancer Res. 2006;66:6990–6997
  253. Yap TA, Olmos D, Brunetto AT, et al. Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies. J. Clin. Oncol. 2011;29:1271–1279
  254. Young RJ, Rischin D, Fisher R, et al. Relationship between epidermal growth factor receptor status, p16INK4A and outcome in head and neck squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 2011;20:1230–1237
  255. Yue P, Turkson J. Targeting STAT3 in cancer: how successful are we?. Expert Opin Investig. Drugs. 2009;18:45–56
  256. Yun CH, Boggon TJ, Li Y, et al. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell. 2007;11:217–227
  257. Zhang Q, Thomas SM, Lui VW, et al. Phosphorylation of TNF-alpha converting enzyme by gastrin-releasing peptide induces amphiregulin release and EGF receptor activation. Proc. Natl. Acad. Sci. U.S.A. 2006;103:6901–6906
  258. Zhang S, Huang WC, Li P, et al. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat. Med. 2011;17:461–469
  259. Zhao D, Wang SH, Feng Y, et al. Intratumoral c-Met expression is associated with vascular endothelial growth factor C expression, lymphangiogenesis, and lymph node metastasis in oral squamous cell carcinoma: implications for use as a prognostic marker. Hum. Pathol. 2011;
  260. Zhao L, Vogt PK. Class I PI3K in oncogenic cellular transformation. Oncogene. 2008;27:5486–5496
  261. Zhou BB, Peyton M, He B, et al. Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer. Cancer Cell. 2006;10:39–50

PII: S1368-7646(11)00061-6

doi: 10.1016/j.drup.2011.08.002

Drug Resistance Updates
Volume 14, Issue 6 , Pages 260-279 , December 2011

Article Tools

* Image Usage & Resolution