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Combination of radiotherapy with EGFR antagonists for head and neck carcinoma

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Abstract

The introduction of biologically sound radiation fractionation regimens and combinations of radiotherapy with chemotherapy have gradually improved both the survival of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and the prospect of organ preservation. Long-term follow-up, however, has shown that some of the radiation–chemotherapy combinations are associated with increased late toxicity. This observation, in conjunction with advances in tumor biology, has led to the launch of investigations into molecular markers and targets for therapeutic interventions. Research on the epidermal growth factor receptor (EGFR)-mediated signaling pathway has enriched our understanding of the biology of HNSCC, in terms of carcinogenesis and cellular processes governing tumor response to therapy. The finding that the addition of an antibody-based inhibitor of the EGFR pathway to radiotherapy significantly improves locoregional control and overall survival rates in patients with locally advanced HNSCC, without increasing radiation-induced toxicity, has resulted in the growing acceptance of such combined regimens as a frontline therapy option for locally advanced HNSCC. Because such therapy has benefited only an additional 10%-15% of patients, studies are being undertaken to identify markers and mechanisms of resistance to EGFR antagonists that are essential for the further refinement of therapy. Overall, preclinical and clinical studies on EGFR have validated the concept that selective tumor radiation sensitization can be achieved by modulating a specific perturbed signaling pathway, and these studies have increased the enthusiasm for developing and investigating other novel agents targeting other cellular processes.

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References

  1. A Jemal R Siegel E Ward et al. (2006) ArticleTitleCancer statistics, 2006 CA Cancer J Clin 56 106–130 Occurrence Handle16514137

    PubMed  Google Scholar 

  2. F Robert MP Ezekiel SA Spencer et al. (2001) ArticleTitlePhase I study of anti-epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer J Clin Oncol 19 3234–3243 Occurrence Handle11432891 Occurrence Handle1:CAS:528:DC%2BD3MXltlShtb8%3D

    PubMed  CAS  Google Scholar 

  3. DO Schneider GF Whitmore (1963) ArticleTitleComparative effects of neutrons and X-rays on mammalian cells Radiat Res 18 286–306 Occurrence Handle13992131 Occurrence Handle1:STN:280:DyaF387otl2qtw%3D%3D Occurrence Handle10.2307/3571497

    Article  PubMed  CAS  Google Scholar 

  4. JJ Kim IF Tannock (2005) ArticleTitleRepopulation of cancer cells during therapy: an important cause of treatment failure Nat Rev Cancer 5 516–525 Occurrence Handle15965493 Occurrence Handle1:CAS:528:DC%2BD2MXmtFOns7c%3D Occurrence Handle10.1038/nrc1650

    Article  PubMed  CAS  Google Scholar 

  5. J Bourhis J Overgaard H Audry et al. (2006) ArticleTitleHyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis Lancet 368 843–854 Occurrence Handle16950362 Occurrence Handle10.1016/S0140-6736(06)69121-6

    Article  PubMed  Google Scholar 

  6. J Bourhis C Armand JP Pignon (2004) ArticleTitleUpdate of MACH-NC (Meta-Analysis of Chemotherapy in Head & Neck Cancer) database focused on concomitant chemoradiotherapy J Clin Oncol ASCO Annual Meeting Proceedings (Post-Meeting Edition) 22 5505

    Google Scholar 

  7. M Al-Sarraf TF Pajak JS Cooper et al. (1990) ArticleTitleChemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma: a Radiation Therapy Oncology Group study J Clin Oncol 8 1342–1351 Occurrence Handle2199621 Occurrence Handle1:STN:280:DyaK3czjvFSqtw%3D%3D

    PubMed  CAS  Google Scholar 

  8. S Cohen (1965) ArticleTitleThe stimulation of epidermal proliferation by a specific protein (EGF) Dev Biol 12 394–407 Occurrence Handle5884352 Occurrence Handle1:CAS:528:DyaF28Xks1Wmug%3D%3D Occurrence Handle10.1016/0012-1606(65)90005-9

    Article  PubMed  CAS  Google Scholar 

  9. S Cohen G Carpenter (1975) ArticleTitleHuman epidermal growth factor: isolation and chemical and biological properties Proc Natl Acad Sci USA 72 1317–1321 Occurrence Handle1055407 Occurrence Handle1:CAS:528:DyaE2MXktVWhtbs%3D Occurrence Handle10.1073/pnas.72.4.1317

    Article  PubMed  CAS  Google Scholar 

  10. S Cohen G Carpenter L King SuffixJr (1980) ArticleTitleEpidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity J Biol Chem 255 4834–4842 Occurrence Handle6246084 Occurrence Handle1:CAS:528:DyaL3cXks1WqsL4%3D

    PubMed  CAS  Google Scholar 

  11. AW Burgess HS Cho C Eigenbrot et al. (2003) ArticleTitleAn open-and-shut case? Recent insights into the activation of EGF/ErbB receptors Mol Cell 12 541–552 Occurrence Handle14527402 Occurrence Handle1:CAS:528:DC%2BD3sXnvFGrsbc%3D Occurrence Handle10.1016/S1097-2765(03)00350-2

    Article  PubMed  CAS  Google Scholar 

  12. SM Thomas FM Coppelli A Wells et al. (2003) ArticleTitleEpidermal growth factor receptor-stimulated activation of phospholipase Cgamma-1 promotes invasion of head and neck squamous cell carcinoma Cancer Res 63 5629–5635 Occurrence Handle14500405 Occurrence Handle1:CAS:528:DC%2BD3sXntlers7Y%3D

    PubMed  CAS  Google Scholar 

  13. S Kalyankrishna JR Grandis (2006) ArticleTitleEpidermal growth factor receptor biology in head and neck cancer J Clin Oncol 24 2666–2672 Occurrence Handle16763281 Occurrence Handle1:CAS:528:DC%2BD28XmslSisbo%3D Occurrence Handle10.1200/JCO.2005.04.8306

    Article  PubMed  CAS  Google Scholar 

  14. WX Schulze L Deng M Mann (2005) ArticleTitlePhosphotyrosine interactome of the ErbB-receptor kinase family Mol Syst Biol 1 2005–0008 Occurrence Handle16729043 Occurrence Handle10.1038/msb4100012 Occurrence Handle1:CAS:528:DC%2BD2MXmtlertb4%3D

    Article  PubMed  CAS  Google Scholar 

  15. R Goldman RB Levy E Peles et al. (1990) ArticleTitleHeterodimerization of the erbB-1 and erbB-2 receptors in human breast carcinoma cells: a mechanism for receptor transregulation Biochemistry 29 11024–11028 Occurrence Handle1980216 Occurrence Handle1:CAS:528:DyaK3cXmt1yltb0%3D Occurrence Handle10.1021/bi00502a002

    Article  PubMed  CAS  Google Scholar 

  16. R Pinkas-Kramarski L Soussan H Waterman et al. (1996) ArticleTitleDiversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions EMBO J 15 2452–2467 Occurrence Handle8665853 Occurrence Handle1:CAS:528:DyaK28XjsVGjurY%3D

    PubMed  CAS  Google Scholar 

  17. Y Yarden (2001) ArticleTitleThe EGFR family and its ligands in human cancer. Signalling mechanisms and therapeutic opportunities Eur J Cancer 37 IssueIDSuppl 4 S3–S8 Occurrence Handle11597398 Occurrence Handle1:CAS:528:DC%2BD3MXntlOku78%3D Occurrence Handle10.1016/S0959-8049(01)00230-1

    Article  PubMed  CAS  Google Scholar 

  18. AP Gilmore AJ Valentijn P Wang et al. (2002) ArticleTitleActivation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor J Biol Chem 277 27643–27650 Occurrence Handle12011069 Occurrence Handle1:CAS:528:DC%2BD38XlvFKgsLo%3D Occurrence Handle10.1074/jbc.M108863200

    Article  PubMed  CAS  Google Scholar 

  19. YN Kim P Dam PJ Bertics (2002) ArticleTitleCaveolin-1 phosphorylation in human squamous and epidermoid carcinoma cells: dependence on ErbB1 expression and Src activation Exp Cell Res 280 134–147 Occurrence Handle12372346 Occurrence Handle1:CAS:528:DC%2BD38XnsVanurk%3D Occurrence Handle10.1006/excr.2002.5623

    Article  PubMed  CAS  Google Scholar 

  20. J Andreev ML Galisteo O Kranenburg et al. (2001) ArticleTitleSrc and Pyk2 mediate G-protein-coupled receptor activation of epidermal growth factor receptor (EGFR) but are not required for coupling to the mitogen-activated protein (MAP) kinase signaling cascade J Biol Chem 276 20130–20135 Occurrence Handle11274221 Occurrence Handle1:CAS:528:DC%2BD3MXktlKnsLw%3D Occurrence Handle10.1074/jbc.M102307200

    Article  PubMed  CAS  Google Scholar 

  21. JE Darnell SuffixJr IM Kerr GR Stark (1994) ArticleTitleJak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins Science 264 1415–1421 Occurrence Handle8197455 Occurrence Handle1:CAS:528:DyaK2cXktlalsL4%3D Occurrence Handle10.1126/science.8197455

    Article  PubMed  CAS  Google Scholar 

  22. T Kijima H Niwa RA Steinman et al. (2002) ArticleTitleSTAT3 activation abrogates growth factor dependence and contributes to head and neck squamous cell carcinoma tumor growth in vivo Cell Growth Differ 13 355–362 Occurrence Handle12193474 Occurrence Handle1:CAS:528:DC%2BD38XmslWjt70%3D

    PubMed  CAS  Google Scholar 

  23. S Xi Q Zhang WE Gooding et al. (2003) ArticleTitleConstitutive activation of Stat5b contributes to carcinogenesis in vivo Cancer Res 63 6763–6771 Occurrence Handle14583472 Occurrence Handle1:CAS:528:DC%2BD3sXosVGnsr4%3D

    PubMed  CAS  Google Scholar 

  24. PM Harari S Huang (2006) ArticleTitleRadiation combined with EGFR signal inhibitors: head and neck cancer focus Semin Radiat Oncol 16 38–44 Occurrence Handle16378905 Occurrence Handle10.1016/j.semradonc.2005.08.005

    Article  PubMed  Google Scholar 

  25. NE Hynes HA Lane (2005) ArticleTitleERBB receptors and cancer: the complexity of targeted inhibitors Nat Rev Cancer 5 341–354 Occurrence Handle15864276 Occurrence Handle1:CAS:528:DC%2BD2MXjslertb0%3D Occurrence Handle10.1038/nrc1609

    Article  PubMed  CAS  Google Scholar 

  26. SY Lin K Makino W Xia et al. (2001) ArticleTitleNuclear localization of EGF receptor and its potential new role as a transcription factor Nat Cell Biol 3 802–808 Occurrence Handle11533659 Occurrence Handle1:CAS:528:DC%2BD3MXmvF2ls74%3D Occurrence Handle10.1038/ncb0901-802

    Article  PubMed  CAS  Google Scholar 

  27. K Dittmann C Mayer B Fehrenbacher et al. (2005) ArticleTitleRadiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase J Biol Chem 280 31182–31189 Occurrence Handle16000298 Occurrence Handle1:CAS:528:DC%2BD2MXpsVCmurs%3D Occurrence Handle10.1074/jbc.M506591200

    Article  PubMed  CAS  Google Scholar 

  28. HW Lo SC Hsu M Ali-Seyed et al. (2005) ArticleTitleNuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway Cancer Cell 7 575–589 Occurrence Handle15950906 Occurrence Handle1:CAS:528:DC%2BD2MXlslCgsrc%3D Occurrence Handle10.1016/j.ccr.2005.05.007

    Article  PubMed  CAS  Google Scholar 

  29. HW Lo MC Hung (2006) ArticleTitleNuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival Br J Cancer 94 184–188 Occurrence Handle16434982 Occurrence Handle1:CAS:528:DC%2BD28XmvVyntQ%3D%3D Occurrence Handle10.1038/sj.bjc.6602941

    Article  PubMed  CAS  Google Scholar 

  30. N Hanada HW Lo CP Day et al. (2006) ArticleTitleCo-regulation of B-Myb expression by E2F1 and EGF receptor Mol Carcinog 45 10–17 Occurrence Handle16299810 Occurrence Handle1:CAS:528:DC%2BD28XntVSrug%3D%3D Occurrence Handle10.1002/mc.20147

    Article  PubMed  CAS  Google Scholar 

  31. KK Khanna SP Jackson (2001) ArticleTitleDNA double-strand breaks: signaling, repair and the cancer connection Nat Genet 27 247–254 Occurrence Handle11242102 Occurrence Handle1:CAS:528:DC%2BD3MXhslKqtLg%3D Occurrence Handle10.1038/85798

    Article  PubMed  CAS  Google Scholar 

  32. CM Warren R Landgraf (2006) ArticleTitleSignaling through ERBB receptors: multiple layers of diversity and control Cell Signal 18 923–933 Occurrence Handle16460914 Occurrence Handle1:CAS:528:DC%2BD28XivVaktbo%3D Occurrence Handle10.1016/j.cellsig.2005.12.007

    Article  PubMed  CAS  Google Scholar 

  33. G Levkowitz H Waterman SA Ettenberg et al. (1999) ArticleTitleUbiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1 Mol Cell 4 1029–1040 Occurrence Handle10635327 Occurrence Handle1:CAS:528:DC%2BD3cXislaqsw%3D%3D Occurrence Handle10.1016/S1097-2765(00)80231-2

    Article  PubMed  CAS  Google Scholar 

  34. HS Wiley (2003) ArticleTitleTrafficking of the ErbB receptors and its influence on signaling Exp Cell Res 284 78–88 Occurrence Handle12648467 Occurrence Handle1:CAS:528:DC%2BD3sXitVylt74%3D Occurrence Handle10.1016/S0014-4827(03)00002-8

    Article  PubMed  CAS  Google Scholar 

  35. JL Boerner ML Demory C Silva et al. (2004) ArticleTitlePhosphorylation of Y845 on the epidermal growth factor receptor mediates binding to the mitochondrial protein cytochrome c oxidase subunit II Mol Cell Biol 24 7059–7071 Occurrence Handle15282306 Occurrence Handle1:CAS:528:DC%2BD2cXmtlOjtrg%3D Occurrence Handle10.1128/MCB.24.16.7059-7071.2004

    Article  PubMed  CAS  Google Scholar 

  36. JR Grandis DJ Tweardy (1993) ArticleTitleElevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer Cancer Res 53 3579–3584 Occurrence Handle8339264 Occurrence Handle1:CAS:528:DyaK3sXmtVSrsbo%3D

    PubMed  CAS  Google Scholar 

  37. J Rubin Grandis MF Melhem EL Barnes et al. (1996) ArticleTitleQuantitative immunohistochemical analysis of transforming growth factor-alpha and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck Cancer 78 1284–1292 Occurrence Handle8826952 Occurrence Handle1:STN:280:DyaK28visVChuw%3D%3D Occurrence Handle10.1002/(SICI)1097-0142(19960915)78:6<1284::AID-CNCR17>3.0.CO;2-X

    Article  PubMed  CAS  Google Scholar 

  38. DM Shin JY Ro WK Hong et al. (1994) ArticleTitleDysregulation of epidermal growth factor receptor expression in premalignant lesions during head and neck tumorigenesis Cancer Res 54 3153–3159 Occurrence Handle8205534 Occurrence Handle1:STN:280:DyaK2c3msFWmuw%3D%3D

    PubMed  CAS  Google Scholar 

  39. J Rubin Grandis Q Zeng DJ Tweardy (1996) ArticleTitleRetinoic acid normalizes the increased gene transcription rate of TGF-alpha and EGFR in head and neck cancer cell lines Nat Med 2 237–240 Occurrence Handle8574972 Occurrence Handle1:STN:280:DyaK287mtVektw%3D%3D Occurrence Handle10.1038/nm0296-237

    Article  PubMed  CAS  Google Scholar 

  40. RK Schmidt-Ullrich RB Mikkelsen P Dent et al. (1997) ArticleTitleRadiation-induced proliferation of the human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation Oncogene 15 1191–1197 Occurrence Handle9294612 Occurrence Handle1:CAS:528:DyaK2sXmt1Gju7k%3D Occurrence Handle10.1038/sj.onc.1201275

    Article  PubMed  CAS  Google Scholar 

  41. JC Sok FM Coppelli SM Thomas et al. (2006) ArticleTitleMutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting Clin Cancer Res 12 5064–5073 Occurrence Handle16951222 Occurrence Handle1:CAS:528:DC%2BD28XovF2hu7Y%3D Occurrence Handle10.1158/1078-0432.CCR-06-0913

    Article  PubMed  CAS  Google Scholar 

  42. CJ Wikstrand RE McLendon AH Friedman et al. (1997) ArticleTitleCell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII Cancer Res 57 4130–4140 Occurrence Handle9307304 Occurrence Handle1:CAS:528:DyaK2sXmtFehtrs%3D

    PubMed  CAS  Google Scholar 

  43. TJ Lynch DW Bell R Sordella et al. (2004) ArticleTitleActivating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib N Engl J Med 350 2129–2139 Occurrence Handle15118073 Occurrence Handle1:CAS:528:DC%2BD2cXktF2js7c%3D Occurrence Handle10.1056/NEJMoa040938

    Article  PubMed  CAS  Google Scholar 

  44. MC Etienne-Grimaldi S Pereira N Magne et al. (2005) ArticleTitleAnalysis of the dinucleotide repeat polymorphism in the epidermal growth factor receptor (EGFR) gene in head and neck cancer patients Ann Oncol 16 934–941 Occurrence Handle15829495 Occurrence Handle10.1093/annonc/mdi189

    Article  PubMed  Google Scholar 

  45. F Cappuzzo M Varella-Garcia H Shigematsu et al. (2005) ArticleTitleIncreased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients J Clin Oncol 23 5007–5018 Occurrence Handle16051952 Occurrence Handle1:CAS:528:DC%2BD2MXpsFWmtLo%3D Occurrence Handle10.1200/JCO.2005.09.111

    Article  PubMed  CAS  Google Scholar 

  46. A Psyrri Z Yu PM Weinberger et al. (2005) ArticleTitleQuantitative determination of nuclear and cytoplasmic epidermal growth factor receptor expression in oropharyngeal squamous cell cancer by using automated quantitative analysis Clin Cancer Res 11 5856–5862 Occurrence Handle16115926 Occurrence Handle1:CAS:528:DC%2BD2MXos1Cjtbg%3D Occurrence Handle10.1158/1078-0432.CCR-05-0420

    Article  PubMed  CAS  Google Scholar 

  47. L Milas T Akimoto NR Hunter et al. (2002) ArticleTitleRelationship between cyclin D1 expression and poor radioresponse of murine carcinomas Int J Radiat Oncol Biol Phys 52 514–521 Occurrence Handle11872299 Occurrence Handle1:CAS:528:DC%2BD38XhtlGlt7c%3D Occurrence Handle10.1016/S0360-3016(01)02693-1

    Article  PubMed  CAS  Google Scholar 

  48. HR Withers JM Taylor B Maciejewski (1988) ArticleTitleThe hazard of accelerated tumor clonogen repopulation during radiotherapy Acta Oncol 27 131–146 Occurrence Handle3390344 Occurrence Handle1:STN:280:DyaL1c3mvFamsw%3D%3D

    PubMed  CAS  Google Scholar 

  49. RK Schmidt-Ullrich K Valerie W Chan et al. (1992) ArticleTitleExpression of oestrogen receptor and transforming growth factor-alpha in MCF-7 cells after exposure to fractionated irradiation Int J Radiat Biol 61 405–415 Occurrence Handle1347074 Occurrence Handle1:CAS:528:DyaK38Xhs12jtL8%3D

    PubMed  CAS  Google Scholar 

  50. BD Kavanagh PS Lin P Chen et al. (1995) ArticleTitleRadiation-induced enhanced proliferation of human squamous cancer cells in vitro: a release from inhibition by epidermal growth factor Clin Cancer Res 1 1557–1562 Occurrence Handle9815956 Occurrence Handle1:CAS:528:DyaK28XmvVWhsA%3D%3D

    PubMed  CAS  Google Scholar 

  51. RK Schmidt-Ullrich JN Contessa G Lammering et al. (2003) ArticleTitleERBB receptor tyrosine kinases and cellular radiation responses Oncogene 22 5855–5865 Occurrence Handle12947392 Occurrence Handle1:CAS:528:DC%2BD3sXmslemtL8%3D Occurrence Handle10.1038/sj.onc.1206698

    Article  PubMed  CAS  Google Scholar 

  52. T Akimoto NR Hunter L Buchmiller et al. (1999) ArticleTitleInverse relationship between epidermal growth factor receptor expression and radiocurability of murine carcinomas Clin Cancer Res 5 2884–2890 Occurrence Handle10537357 Occurrence Handle1:CAS:528:DyaK1MXntlGlur0%3D

    PubMed  CAS  Google Scholar 

  53. KK Ang BA Berkey X Tu et al. (2002) ArticleTitleImpact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma Cancer Res 62 7350–7356 Occurrence Handle12499279 Occurrence Handle1:CAS:528:DC%2BD3sXhtV2juw%3D%3D

    PubMed  CAS  Google Scholar 

  54. K Liang KK Ang L Milas et al. (2003) ArticleTitleThe epidermal growth factor receptor mediates radioresistance Int J Radiat Oncol Biol Phys 57 246–254 Occurrence Handle12909240 Occurrence Handle1:CAS:528:DC%2BD3sXlvFGktbc%3D Occurrence Handle10.1016/S0360-3016(03)00511-X

    Article  PubMed  CAS  Google Scholar 

  55. J Mendelsohn H Masui A Goldenberg (1987) ArticleTitleAnti-epidermal growth factor receptor monoclonal antibodies may inhibit A431 tumor cell proliferation by blocking an autocrine pathway Trans Assoc Am Physicians 100 173–178 Occurrence Handle3502661 Occurrence Handle1:CAS:528:DyaL1cXktlaitr0%3D

    PubMed  CAS  Google Scholar 

  56. JD Sato T Kawamoto AD Le et al. (1983) ArticleTitleBiological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors Mol Biol Med 1 511–529 Occurrence Handle6094961 Occurrence Handle1:CAS:528:DyaL2cXls1Cgu70%3D

    PubMed  CAS  Google Scholar 

  57. N Balaban J Moni M Shannon et al. (1996) ArticleTitleThe effect of ionizing radiation on signal transduction: antibodies to EGF receptor sensitize A431 cells to radiation Biochim Biophys Acta 1314 147–156 Occurrence Handle8972728 Occurrence Handle1:CAS:528:DyaK28XmvFaksrw%3D Occurrence Handle10.1016/S0167-4889(96)00068-7

    Article  PubMed  CAS  Google Scholar 

  58. MN Saleh KP Raisch MA Stackhouse et al. (1999) ArticleTitleCombined modality therapy of A431 human epidermoid cancer using anti-EGFr antibody C225 and radiation Cancer Biother Radiopharm 14 451–463 Occurrence Handle10850332 Occurrence Handle1:CAS:528:DC%2BD3cXivF2ntQ%3D%3D

    PubMed  CAS  Google Scholar 

  59. SM Huang JM Bock PM Harari (1999) ArticleTitleEpidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck Cancer Res 59 1935–1940 Occurrence Handle10213503 Occurrence Handle1:CAS:528:DyaK1MXislejtrc%3D

    PubMed  CAS  Google Scholar 

  60. SM Huang PM Harari (1999) ArticleTitleEpidermal growth factor receptor inhibition in cancer therapy: biology, rationale and preliminary clinical results Invest New Drugs 17 259–269 Occurrence Handle10665478 Occurrence Handle1:CAS:528:DC%2BD3cXhtFart7c%3D Occurrence Handle10.1023/A:1006384521198

    Article  PubMed  CAS  Google Scholar 

  61. L Milas K Mason N Hunter et al. (2000) ArticleTitleIn vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody Clin Cancer Res 6 701–708 Occurrence Handle10690556 Occurrence Handle1:CAS:528:DC%2BD3cXhs1akt7c%3D

    PubMed  CAS  Google Scholar 

  62. S Nasu KK Ang Z Fan et al. (2001) ArticleTitleC225 antiepidermal growth factor receptor antibody enhances tumor radiocurability Int J Radiat Oncol Biol Phys 51 474–477 Occurrence Handle11567823 Occurrence Handle1:CAS:528:DC%2BD3MXmvVyltbc%3D Occurrence Handle10.1016/S0360-3016(01)01671-6

    Article  PubMed  CAS  Google Scholar 

  63. C Bianco G Tortora R Bianco et al. (2002) ArticleTitleEnhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa) Clin Cancer Res 8 3250–3258 Occurrence Handle12374696 Occurrence Handle1:CAS:528:DC%2BD38XosFKhtrc%3D

    PubMed  CAS  Google Scholar 

  64. Y She F Lee J Chen et al. (2003) ArticleTitleThe epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 selectively potentiates radiation response of human tumors in nude mice, with a marked improvement in therapeutic index Clin Cancer Res 9 3773–3778 Occurrence Handle14506170 Occurrence Handle1:CAS:528:DC%2BD3sXosVOks7w%3D

    PubMed  CAS  Google Scholar 

  65. P Chinnaiyan S Huang G Vallabhaneni et al. (2005) ArticleTitleMechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva) Cancer Res 65 3328–3335 Occurrence Handle15833866 Occurrence Handle1:CAS:528:DC%2BD2MXjt1yrsrc%3D

    PubMed  CAS  Google Scholar 

  66. B Solomon J Hagekyriakou MK Trivett et al. (2003) ArticleTitleEGFR blockade with ZD1839 (“Iressa”) potentiates the antitumor effects of single and multiple fractions of ionizing radiation in human A431 squamous cell carcinoma Int J Radiat Oncol Biol Phys 55 713–723 Occurrence Handle12573759 Occurrence Handle1:CAS:528:DC%2BD3sXptFGhug%3D%3D Occurrence Handle10.1016/S0360-3016(02)04357-2

    Article  PubMed  CAS  Google Scholar 

  67. SM Huang PM Harari (2000) ArticleTitleModulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis Clin Cancer Res 6 2166–2174 Occurrence Handle10873065 Occurrence Handle1:CAS:528:DC%2BD3cXksVGhsrw%3D

    PubMed  CAS  Google Scholar 

  68. SM Huang J Li PM Harari (2002) ArticleTitleMolecular inhibition of angiogenesis and metastatic potential in human squamous cell carcinomas after epidermal growth factor receptor blockade Mol Cancer Ther 1 507–514 Occurrence Handle12479268 Occurrence Handle1:CAS:528:DC%2BD38XktlSksbs%3D

    PubMed  CAS  Google Scholar 

  69. M Baumann M Krause (2004) ArticleTitleTargeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results Radiother Oncol 72 257–266 Occurrence Handle15450723 Occurrence Handle1:CAS:528:DC%2BD2cXnvV2murY%3D Occurrence Handle10.1016/j.radonc.2004.07.007

    Article  PubMed  CAS  Google Scholar 

  70. JA Bonner KP Raisch HQ Trummell et al. (2000) ArticleTitleEnhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation in head and neck cancers J Clin Oncol 18 47S–53S Occurrence Handle11060327 Occurrence Handle1:CAS:528:DC%2BD3cXot1ant7Y%3D

    PubMed  CAS  Google Scholar 

  71. EK Rowinsky (2004) ArticleTitleThe erbB family: targets for therapeutic development against cancer and therapeutic strategies using monoclonal antibodies and tyrosine kinase inhibitors Annu Rev Med 55 433–457 Occurrence Handle14746530 Occurrence Handle1:CAS:528:DC%2BD2cXitVWru74%3D Occurrence Handle10.1146/annurev.med.55.091902.104433

    Article  PubMed  CAS  Google Scholar 

  72. S Li KR Schmitz PD Jeffrey et al. (2005) ArticleTitleStructural basis for inhibition of the epidermal growth factor receptor by cetuximab Cancer Cell 7 301–311 Occurrence Handle15837620 Occurrence Handle1:CAS:528:DC%2BD2MXjvFSkurk%3D Occurrence Handle10.1016/j.ccr.2005.03.003

    Article  PubMed  CAS  Google Scholar 

  73. P Dent DB Reardon JS Park et al. (1999) ArticleTitleRadiation-induced release of transforming growth factor alpha activates the epidermal growth factor receptor and mitogen-activated protein kinase pathway in carcinoma cells, leading to increased proliferation and protection from radiation-induced cell death Mol Biol Cell 10 2493–2506 Occurrence Handle10436007 Occurrence Handle1:CAS:528:DyaK1MXlsVyrurg%3D

    PubMed  CAS  Google Scholar 

  74. JA Bonner PM Harari J Giralt et al. (2006) ArticleTitleRadiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck N Engl J Med 354 567–578 Occurrence Handle16467544 Occurrence Handle1:CAS:528:DC%2BD28Xhtleksbs%3D Occurrence Handle10.1056/NEJMoa053422

    Article  PubMed  CAS  Google Scholar 

  75. PM Harari GK Hartig (2003) ArticleTitleImpact of the EGFR inhibitor C225 on wound healing in advanced head and neck cancer patients undergoing neck dissection J Clin Oncol. ASCO Annual Meeting Proceedings (Post-Meeting Edition) 22 220

    Google Scholar 

  76. JA Bonner J Giralt (2005) ArticleTitleImproved preservation of larynx with the addition of cetuximab to radiation of cetuximab for cancers of the larynx and hypopharynx J Clin Oncol. ASCO Annual Meeting Proceedings (Post-Meeting Edition) 23 5533

    Google Scholar 

  77. DG Pfister YB Su DH Kraus et al. (2006) ArticleTitleConcurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm J Clin Oncol 24 1072–1078 Occurrence Handle16505426 Occurrence Handle1:CAS:528:DC%2BD28XislGgsbo%3D Occurrence Handle10.1200/JCO.2004.00.1792

    Article  PubMed  CAS  Google Scholar 

  78. De La Garza JG, Granados M, Aguilar JL, et al. (2006) Phase II clinical trial preliminary report: Cetuximab, gemcitabine and simultaneous radiotherapy for locally advanced head and neck cancer: Preliminary report J Clin Oncol. ASCO Annual Meeting Proceedings (Post-Meeting Edition) 24:15 502

  79. DT Chua JM Nicholls JS Sham et al. (2004) ArticleTitlePrognostic value of epidermal growth factor receptor expression in patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy and radiotherapy Int J Radiat Oncol Biol Phys 59 11–20 Occurrence Handle15093894 Occurrence Handle1:CAS:528:DC%2BD2cXjt1Sisbo%3D Occurrence Handle10.1016/j.ijrobp.2003.10.038

    Article  PubMed  CAS  Google Scholar 

  80. SM Bentzen BM Atasoy FM Daley et al. (2005) ArticleTitleEpidermal growth factor receptor expression in pretreatment biopsies from head and neck squamous cell carcinoma as a predictive factor for a benefit from accelerated radiation therapy in a randomized controlled trial J Clin Oncol 23 5560–5567 Occurrence Handle16110017 Occurrence Handle1:CAS:528:DC%2BD2MXhtVersr%2FI Occurrence Handle10.1200/JCO.2005.06.411

    Article  PubMed  CAS  Google Scholar 

  81. JG Eriksen T Steiniche J Askaa et al. (2004) ArticleTitleThe prognostic value of epidermal growth factor receptor is related to tumor differentiation and the overall treatment time of radiotherapy in squamous cell carcinomas of the head and neck Int J Radiat Oncol Biol Phys 58 561–566 Occurrence Handle14751528 Occurrence Handle1:CAS:528:DC%2BD2cXnvVKksw%3D%3D Occurrence Handle10.1016/j.ijrobp.2003.09.043

    Article  PubMed  CAS  Google Scholar 

  82. A Psyrri G Fountzilas (2006) ArticleTitleAdvances in the treatment of locally advanced non-nasopharyngeal squamous cell carcinoma of the head and neck region Med Oncol 23 1–15 Occurrence Handle16645225 Occurrence Handle1:CAS:528:DC%2BD28XktVOntL4%3D Occurrence Handle10.1385/MO:23:1:1

    Article  PubMed  CAS  Google Scholar 

  83. B Burtness MA Goldwasser W Flood et al. (2005) ArticleTitlePhase 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 23 8646–8654 Occurrence Handle16314626 Occurrence Handle10.1200/JCO.2005.02.4646

    Article  PubMed  Google Scholar 

  84. D Soulieres NN Senzer EE Vokes et al. (2004) ArticleTitleMulticenter 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 22 77–85 Occurrence Handle14701768 Occurrence Handle1:CAS:528:DC%2BD2cXpsVKiurk%3D Occurrence Handle10.1200/JCO.2004.06.075

    Article  PubMed  CAS  Google Scholar 

  85. L Saltz (2005) ArticleTitleEpidermal growth factor receptor-negative colorectal cancer: is there truly such an entity? Clin Colorectal Cancer 5 IssueIDSuppl 2 S98–S100 Occurrence Handle16336755 Occurrence Handle1:CAS:528:DC%2BD2MXhtlaisL7E

    PubMed  CAS  Google Scholar 

  86. KY Chung J Shia NE Kemeny et al. (2005) ArticleTitleCetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry J Clin Oncol 23 1803–1810 Occurrence Handle15677699 Occurrence Handle1:CAS:528:DC%2BD2MXjt1Ckuro%3D Occurrence Handle10.1200/JCO.2005.08.037

    Article  PubMed  CAS  Google Scholar 

  87. R Dziadziuszko FR Hirsch M Varella-Garcia et al. (2006) ArticleTitleSelecting lung cancer patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors by immunohistochemistry and fluorescence in situ hybridization – why, when, and how? Clin Cancer Res 12 4409s–4415s Occurrence Handle16857819 Occurrence Handle1:CAS:528:DC%2BD28XntFSmtrw%3D Occurrence Handle10.1158/1078-0432.CCR-06-0087

    Article  PubMed  CAS  Google Scholar 

  88. J Loeffler-Ragg M Witsch-Baumgartner A Tzankov et al. (2006) ArticleTitleLow incidence of mutations in EGFR kinase domain in Caucasian patients with head and neck squamous cell carcinoma Eur J Cancer 42 109–111 Occurrence Handle16324836 Occurrence Handle1:CAS:528:DC%2BD2MXhtlCktLzO Occurrence Handle10.1016/j.ejca.2005.08.034

    Article  PubMed  CAS  Google Scholar 

  89. JS Lee JS Ro A Eisbruch et al. (1988) ArticleTitleMultiple restriction fragment length polymorphisms of the human epidermal growth factor receptor gene Cancer Res 48 4045–4048 Occurrence Handle2898288 Occurrence Handle1:CAS:528:DyaL1cXltVGkur8%3D

    PubMed  CAS  Google Scholar 

  90. EE Cohen F Rosen WM Stadler et al. (2003) ArticleTitlePhase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck J Clin Oncol 21 1980–1987 Occurrence Handle12743152 Occurrence Handle1:CAS:528:DC%2BD2cXptlCksbk%3D Occurrence Handle10.1200/JCO.2003.10.051

    Article  PubMed  CAS  Google Scholar 

  91. TB Gibson A Ranganathan A Grothey (2006) ArticleTitleRandomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer Clin Colorectal Cancer 6 29–31 Occurrence Handle16796788 Occurrence Handle10.3816/CCC.2006.n.01

    Article  PubMed  Google Scholar 

  92. J Baselga JM Trigo J Bourhis et al. (2005) ArticleTitlePhase 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 23 5568–5577 Occurrence Handle16009950 Occurrence Handle1:CAS:528:DC%2BD2MXhtVersr%2FJ Occurrence Handle10.1200/JCO.2005.07.119

    Article  PubMed  CAS  Google Scholar 

  93. NW Choong EE Cohen (2006) ArticleTitleEpidermal growth factor receptor directed therapy in head and neck cancer Crit Rev Oncol Hematol 57 25–43 Occurrence Handle16207530

    PubMed  Google Scholar 

  94. L Milas F Fang KA Mason et al. (2007) ArticleTitleImportance of maintenance therapy in C225-induced enhancement of tumor control by fractionated radiation Int J Radiat Oncol Biol Phys 1 IssueID67 568–572

    Google Scholar 

  95. T Crombet M Osorio T Cruz et al. (2004) ArticleTitleUse of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients J Clin Oncol 22 1646–1654 Occurrence Handle15117987 Occurrence Handle10.1200/JCO.2004.03.089 Occurrence Handle1:CAS:528:DC%2BD2cXpsVWlsr8%3D

    Article  PubMed  CAS  Google Scholar 

  96. DH Lynch XD Yang (2002) ArticleTitleTherapeutic potential of ABX-EGF: a fully human anti-epidermal growth factor receptor monoclonal antibody for cancer treatment Semin Oncol 29 47–50 Occurrence Handle11894013 Occurrence Handle1:CAS:528:DC%2BD38XjtVKjsrw%3D Occurrence Handle10.1053/sonc.2002.31522

    Article  PubMed  CAS  Google Scholar 

  97. EE Cohen (2006) ArticleTitleRole of epidermal growth factor receptor pathway-targeted therapy in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck J Clin Oncol 24 2659–2665 Occurrence Handle16763280 Occurrence Handle1:CAS:528:DC%2BD28XmslSisb0%3D Occurrence Handle10.1200/JCO.2005.05.4577

    Article  PubMed  CAS  Google Scholar 

  98. D Herchenhorn FL Dias CG Ferreira et al. (2006) ArticleTitlePhase I/II study of erlotinib combined with cisplatin and radiotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN) J Clin Oncol ASCO Annual Meeting Proceedings (Post-Meeting Edition) 24 5575

    Google Scholar 

  99. P Savvides SS Agarwala J Greskovich et al. (2006) ArticleTitlePhase I study of the EGFR tyrosine kinase inhibitor erlotinib in combination with docetaxel and radiation in locally advanced squamous cell cancer of the head and neck (SCCHN) J Clin Oncol ASCO Annual Meeting Proceedings (Post-Meeting Edition) 24 5545

    Google Scholar 

  100. CT Allen EA Donovan Z Chen et al. (2006) ArticleTitleClinical, signaling pathway, and cellular effects of epidermal growth factor receptor (EGFR) inhibition with gefitinib in combination with paclitaxel and radiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) J Clin Oncol ASCO Annual Meeting Proceedings (Post-Meeting Edition) 24 15540

    Google Scholar 

  101. HH Doss FA Greco AA Meluch et al. (2006) ArticleTitleInduction chemotherapy + gefitinib followed by concurrent chemotherapy/radiation therapy/gefitinib for patients (pts) with locally advanced squamous carcinoma of the head and neck: A phase I/II trial of the Minnie Pearl Cancer Research Network J Clin Oncol ASCO Annual Meeting Proceedings (Post-Meeting Edition) 24 5543

    Google Scholar 

  102. TS Lawrence MK Nyati (2002) ArticleTitleSmall-molecule tyrosine kinase inhibitors as radiosensitizers Semin Radiat Oncol 12 33–36 Occurrence Handle12174343 Occurrence Handle10.1053/srao.2002.34867

    Article  PubMed  Google Scholar 

  103. MK Nyati D Maheshwari S Hanasoge et al. (2004) ArticleTitleRadiosensitization by pan ErbB inhibitor CI-1033 in vitro and in vivo Clin Cancer Res 10 691–700 Occurrence Handle14760092 Occurrence Handle1:CAS:528:DC%2BD2cXovVKjtw%3D%3D Occurrence Handle10.1158/1078-0432.CCR-1041-03

    Article  PubMed  CAS  Google Scholar 

  104. MR Dewji (2004) ArticleTitleEarly phase I data on an irreversible pan-erb inhibitor: CI-1033. What did we learn? J Chemother 16 IssueIDSuppl 4 44–48 Occurrence Handle15688609 Occurrence Handle1:CAS:528:DC%2BD2MXhsFantLc%3D

    PubMed  CAS  Google Scholar 

  105. E Calvo AW Tolcher LA Hammond et al. (2004) ArticleTitleAdministration of CI-1033, an irreversible pan-erbB tyrosine kinase inhibitor, is feasible on a 7-day on, 7-day off schedule: a phase I pharmacokinetic and food effect study Clin Cancer Res 10 7112–7120 Occurrence Handle15534081 Occurrence Handle1:CAS:528:DC%2BD2cXpsVKltL4%3D Occurrence Handle10.1158/1078-0432.CCR-04-1187

    Article  PubMed  CAS  Google Scholar 

  106. J Nemunaitis I Eiseman C Cunningham et al. (2005) ArticleTitlePhase 1 clinical and pharmacokinetics evaluation of oral CI-1033 in patients with refractory cancer Clin Cancer Res 11 3846–3853 Occurrence Handle15897585 Occurrence Handle1:CAS:528:DC%2BD2MXktFyru7Y%3D Occurrence Handle10.1158/1078-0432.CCR-04-1950

    Article  PubMed  CAS  Google Scholar 

  107. S Campos O Hamid MV Seiden et al. (2005) ArticleTitleMulticenter, randomized phase II trial of oral CI-1033 for previously treated advanced ovarian cancer J Clin Oncol 23 5597–5604 Occurrence Handle16110019 Occurrence Handle1:CAS:528:DC%2BD2MXhtVersr%2FL Occurrence Handle10.1200/JCO.2005.08.091

    Article  PubMed  CAS  Google Scholar 

  108. LL Garland M Hidalgo DS Mendelson et al. (2006) ArticleTitleA phase I clinical and pharmacokinetic study of oral CI-1033 in combination with docetaxel in patients with advanced solid tumors Clin Cancer Res 12 4274–4282 Occurrence Handle16857802 Occurrence Handle1:CAS:528:DC%2BD28XntFSmsLg%3D Occurrence Handle10.1158/1078-0432.CCR-05-2507

    Article  PubMed  CAS  Google Scholar 

  109. ER Wood AT Truesdale OB McDonald et al. (2004) ArticleTitleA unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells Cancer Res 64 6652–6659 Occurrence Handle15374980 Occurrence Handle1:CAS:528:DC%2BD2cXnsFOlu7g%3D Occurrence Handle10.1158/0008-5472.CAN-04-1168

    Article  PubMed  CAS  Google Scholar 

  110. Harrington K, Bourhis J, Nutting CM, et al. (2006) A phase I, open-label study of lapatinib plus chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

  111. P Matar F Rojo R Cassia et al. (2004) ArticleTitleCombined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225): superiority over single-agent receptor targeting Clin Cancer Res 10 6487–6501 Occurrence Handle15475436 Occurrence Handle1:CAS:528:DC%2BD2cXot1OitbY%3D Occurrence Handle10.1158/1078-0432.CCR-04-0870

    Article  PubMed  CAS  Google Scholar 

  112. S Huang EA Armstrong S Benavente et al. (2004) ArticleTitleDual-agent molecular targeting of the epidermal growth factor receptor (EGFR): combining anti-EGFR antibody with tyrosine kinase inhibitor Cancer Res 64 5355–5362 Occurrence Handle15289342 Occurrence Handle1:CAS:528:DC%2BD2cXmtF2murY%3D Occurrence Handle10.1158/0008-5472.CAN-04-0562

    Article  PubMed  CAS  Google Scholar 

  113. J Baselga P Schöffski F Rojo et al. (2006) ArticleTitleA phase I pharmacokinetic (PK) and molecular pharmacodynamic (PD) study of the combination of two anti-EGFR therapies, the monoclonal antibody (MAb) cetuximab (C) and the tyrosine kinase inhibitor (TKI) gefitinib (G), in patients (pts) with advanced colorectal (CRC), head and neck (HNC) and non-small cell lung cancer (NSCLC) J Clin Oncol. ASCO Annual Meeting Proceedings (Post-Meeting Edition) 24 3006

    Google Scholar 

  114. D Lee (2005) ArticleTitlePhase II data with ZD6474, a small-molecule kinase inhibitor of epidermal growth factor receptor and vascular endothelial growth factor receptor, in previously treated advanced non-small-cell lung cancer Clin Lung Cancer 7 89–91 Occurrence Handle16179094

    PubMed  Google Scholar 

  115. MW Pedersen M Meltorn L Damstrup et al. (2001) ArticleTitleThe type III epidermal growth factor receptor mutation. Biological significance and potential target for anti-cancer therapy Ann Oncol 12 745–760 Occurrence Handle11484948 Occurrence Handle1:STN:280:DC%2BD38%2FislSktw%3D%3D Occurrence Handle10.1023/A:1011177318162

    Article  PubMed  CAS  Google Scholar 

  116. G Lammering TH Hewit K Valerie et al. (2003) ArticleTitleEGFRvIII-mediated radioresistance through a strong cytoprotective response Oncogene 22 5545–5553 Occurrence Handle12944901 Occurrence Handle1:CAS:528:DC%2BD3sXmslSjtb4%3D Occurrence Handle10.1038/sj.onc.1206788

    Article  PubMed  CAS  Google Scholar 

  117. M Zhan ZC Han (2004) ArticleTitlePhosphatidylinositide 3-kinase/AKT in radiation responses Histol Histopathol 19 915–923 Occurrence Handle15168354 Occurrence Handle1:CAS:528:DC%2BD2cXntVygur0%3D

    PubMed  CAS  Google Scholar 

  118. JM Pedrero DG Carracedo CM Pinto et al. (2005) ArticleTitleFrequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma Int J Cancer 114 242–248 Occurrence Handle15543611 Occurrence Handle1:CAS:528:DC%2BD2MXhtFOksro%3D Occurrence Handle10.1002/ijc.20711

    Article  PubMed  CAS  Google Scholar 

  119. K Okami L Wu G Riggins et al. (1998) ArticleTitleAnalysis of PTEN/MMAC1 alterations in aerodigestive tract tumors Cancer Res 58 509–511 Occurrence Handle9458098 Occurrence Handle1:STN:280:DyaK1c7hslejsA%3D%3D

    PubMed  CAS  Google Scholar 

  120. AB Motoyama NE Hynes HA Lane (2002) ArticleTitleThe efficacy of ErbB receptor-targeted anticancer therapeutics is influenced by the availability of epidermal growth factor-related peptides Cancer Res 62 3151–3158 Occurrence Handle12036928 Occurrence Handle1:CAS:528:DC%2BD38XksVyqs70%3D

    PubMed  CAS  Google Scholar 

  121. A Hurbin L Dubrez JL Coll et al. (2002) ArticleTitleInhibition of apoptosis by amphiregulin via an insulin-like growth factor-1 receptor-dependent pathway in non-small cell lung cancer cell lines J Biol Chem 277 49127–49133 Occurrence Handle12356750 Occurrence Handle1:CAS:528:DC%2BD38XpsFaltbs%3D Occurrence Handle10.1074/jbc.M207584200

    Article  PubMed  CAS  Google Scholar 

  122. A Chakravarti JS Loeffler NJ Dyson (2002) ArticleTitleInsulin-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 62 200–207 Occurrence Handle11782378 Occurrence Handle1:CAS:528:DC%2BD38XntV2hsA%3D%3D

    PubMed  CAS  Google Scholar 

  123. H Daub FU Weiss C Wallasch et al. (1996) ArticleTitleRole of transactivation of the EGF receptor in signalling by G-protein-coupled receptors Nature 379 557–560 Occurrence Handle8596637 Occurrence Handle1:CAS:528:DyaK28XhtVWhtr4%3D Occurrence Handle10.1038/379557a0

    Article  PubMed  CAS  Google Scholar 

  124. S Thomas AQZ Wentzel (2005) ArticleTitleProstaglandin E2 and bradykinin contribute to head and neck squamous cell carcinoma carcinogenesis via EGFR dependent and independent mechanisms Proc Am Assoc Cancer Res 46 169

    Google Scholar 

  125. S Hart OM Fischer N Prenzel et al. (2005) ArticleTitleGPCR-induced migration of breast carcinoma cells depends on both EGFR signal transactivation and EGFR-independent pathways Biol Chem 386 845–855 Occurrence Handle16164409 Occurrence Handle1:CAS:528:DC%2BD2MXhtVygs7nN Occurrence Handle10.1515/BC.2005.099

    Article  PubMed  CAS  Google Scholar 

  126. K Krysan KL Reckamp H Dalwadi et al. (2005) ArticleTitleProstaglandin E2 activates mitogen-activated protein kinase/Erk pathway signaling and cell proliferation in non-small cell lung cancer cells in an epidermal growth factor receptor-independent manner Cancer Res 65 6275–6281 Occurrence Handle16024629 Occurrence Handle1:CAS:528:DC%2BD2MXmt1egsL0%3D Occurrence Handle10.1158/0008-5472.CAN-05-0216

    Article  PubMed  CAS  Google Scholar 

  127. G Bowers D Reardon T Hewitt et al. (2001) ArticleTitleThe relative role of ErbB1–4 receptor tyrosine kinases in radiation signal transduction responses of human carcinoma cells Oncogene 20 1388–1397 Occurrence Handle11313882 Occurrence Handle1:CAS:528:DC%2BD3MXisFWgsrg%3D Occurrence Handle10.1038/sj.onc.1204255

    Article  PubMed  CAS  Google Scholar 

  128. C Wild-Bode M Weller A Rimner et al. (2001) ArticleTitleSublethal irradiation promotes migration and invasiveness of glioma cells: implications for radiotherapy of human glioblastoma Cancer Res 61 2744–2750 Occurrence Handle11289157 Occurrence Handle1:CAS:528:DC%2BD3MXisVSksbs%3D

    PubMed  CAS  Google Scholar 

  129. RJ Eisma JD Spiro DL Kreutzer (1997) ArticleTitleVascular endothelial growth factor expression in head and neck squamous cell carcinoma Am J Surg 174 513–517 Occurrence Handle9374227 Occurrence Handle1:CAS:528:DyaK2sXnsFSqu7o%3D Occurrence Handle10.1016/S0002-9610(97)00166-9

    Article  PubMed  CAS  Google Scholar 

  130. A Viloria-Petit T Crombet S Jothy et al. (2001) ArticleTitleAcquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis Cancer Res 61 5090–5101 Occurrence Handle11431346 Occurrence Handle1:CAS:528:DC%2BD3MXltVequ70%3D

    PubMed  CAS  Google Scholar 

  131. Y Lu X Zi Y Zhao et al. (2001) ArticleTitleInsulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin) J Natl Cancer Inst 93 1852–1857 Occurrence Handle11752009 Occurrence Handle1:CAS:528:DC%2BD38XltVWluw%3D%3D Occurrence Handle10.1093/jnci/93.24.1852

    Article  PubMed  CAS  Google Scholar 

  132. JR Tonra DS Deevi E Corcoran et al. (2006) ArticleTitleSynergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy Clin Cancer Res 12 2197–2207 Occurrence Handle16609035 Occurrence Handle1:CAS:528:DC%2BD28XjtlChs7k%3D Occurrence Handle10.1158/1078-0432.CCR-05-1682

    Article  PubMed  CAS  Google Scholar 

  133. P Traxler PR Allegrini R Brandt et al. (2004) ArticleTitleAEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity Cancer Res 64 4931–4941 Occurrence Handle15256466 Occurrence Handle1:CAS:528:DC%2BD2cXls1Omtrc%3D Occurrence Handle10.1158/0008-5472.CAN-03-3681

    Article  PubMed  CAS  Google Scholar 

  134. LF Hennequin AP Thomas C Johnstone et al. (1999) ArticleTitleDesign and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors J Med Chem 42 5369–5389 Occurrence Handle10639280 Occurrence Handle1:CAS:528:DyaK1MXnvVCmur4%3D Occurrence Handle10.1021/jm990345w

    Article  PubMed  CAS  Google Scholar 

  135. OG Yigitbasi MN Younes D Doan et al. (2004) ArticleTitleTumor cell and endothelial cell therapy of oral cancer by dual tyrosine kinase receptor blockade Cancer Res 64 7977–7984 Occurrence Handle15520205 Occurrence Handle1:CAS:528:DC%2BD2cXptFels7o%3D Occurrence Handle10.1158/0008-5472.CAN-04-1477

    Article  PubMed  CAS  Google Scholar 

  136. SR Wedge DJ Ogilvie M Dukes et al. (2002) ArticleTitleZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration Cancer Res 62 4645–4655 Occurrence Handle12183421 Occurrence Handle1:CAS:528:DC%2BD38XmsVShsL8%3D

    PubMed  CAS  Google Scholar 

  137. F Ciardiello R Caputo V Damiano et al. (2003) ArticleTitleAntitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase Clin Cancer Res 9 1546–1556 Occurrence Handle12684431 Occurrence Handle1:CAS:528:DC%2BD3sXislerur8%3D

    PubMed  CAS  Google Scholar 

  138. KJ Williams BA Telfer S Brave et al. (2004) ArticleTitleZD6474, a potent inhibitor of vascular endothelial growth factor signaling, combined with radiotherapy: schedule-dependent enhancement of antitumor activity Clin Cancer Res 10 8587–8593 Occurrence Handle15623642 Occurrence Handle1:CAS:528:DC%2BD2cXhtFGjs7bK Occurrence Handle10.1158/1078-0432.CCR-04-1147

    Article  PubMed  CAS  Google Scholar 

  139. MP Morelli T Cascone T Troiani et al. (2006) ArticleTitleAnti-tumor activity of the combination of cetuximab, an anti-EGFR blocking monoclonal antibody and ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases J Cell Physiol 208 344–353 Occurrence Handle16688779 Occurrence Handle1:CAS:528:DC%2BD28XmvVKisbc%3D Occurrence Handle10.1002/jcp.20666

    Article  PubMed  CAS  Google Scholar 

  140. WD Brazelle W Shi DW Siemann (2006) ArticleTitleVEGF-associated tyrosine kinase inhibition increases the tumor response to single and fractionated dose radiotherapy Int J Radiat Oncol Biol Phys 65 836–841 Occurrence Handle16751064 Occurrence Handle1:CAS:528:DC%2BD28XltlGrtbs%3D

    PubMed  CAS  Google Scholar 

  141. EL Kwak R Sordella DW Bell et al. (2005) ArticleTitleIrreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib Proc Natl Acad Sci USA 102 7665–7670 Occurrence Handle15897464 Occurrence Handle1:CAS:528:DC%2BD2MXkslOmsr0%3D Occurrence Handle10.1073/pnas.0502860102

    Article  PubMed  CAS  Google Scholar 

  142. MP Morelli T Cascone T Troiani et al. (2006) ArticleTitleAntitumor activity of the combination of cetuximab, an anti-EGFR blocking monoclonal antibody and ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases J Clin Oncol. ASCO Annual Meeting Proceedings (Post-Meeting Edition) 24 131

    Google Scholar 

  143. JV Heymach (2005) ArticleTitleZD6474–clinical experience to date Br J Cancer 92 IssueIDSuppl 1 S14–20 Occurrence Handle15928653 Occurrence Handle1:CAS:528:DC%2BD2MXks1Gnt7c%3D Occurrence Handle10.1038/sj.bjc.6602604

    Article  PubMed  CAS  Google Scholar 

  144. SN Holden SG Eckhardt R Basser et al. (2005) ArticleTitleClinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors Ann Oncol 16 1391–1397 Occurrence Handle15905307 Occurrence Handle1:STN:280:DC%2BD2MzotFalsQ%3D%3D Occurrence Handle10.1093/annonc/mdi247

    Article  PubMed  CAS  Google Scholar 

  145. SK Williamson J Moon CH Huang et al. (2006) ArticleTitleA phase II trial of BAY 43-9006 in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC): A Southwest Oncology Group (SWOG) trial J Clin Oncol. ASCO Annual Meeting Proceedings (Post-Meeting Edition) 24 5550

    Google Scholar 

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Authors and Affiliations

  1. Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Juliette Thariat, Kathryn A. Mason & Luka Milas

  2. Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Box 97, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Gokcen Yildirim, Adam S. Garden & K. Kian Ang

Authors
  1. Juliette Thariat
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  2. Gokcen Yildirim
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  3. Kathryn A. Mason
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  4. Adam S. Garden
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  5. Luka Milas
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Correspondence to K. Kian Ang.

Additional information

Dr. L. Milas has received research funding from Imclone Systems Inc. and Sanofi-Aventis.

Dr. K.K. Ang has served on Advisory Boards of AstraZeneca, Bristol-Myers Squibb, Imclone Systems Inc., and Sanofi-Aventis.

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Thariat, J., Yildirim, G., Mason, K. et al. Combination of radiotherapy with EGFR antagonists for head and neck carcinoma. Int J Clin Oncol 12, 99–110 (2007). https://doi.org/10.1007/s10147-006-0663-5

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