Radiotherapy & Oncology
Volume 97, Issue 2 , Pages 322-329 , November 2010

Effect of cetuximab and fractionated irradiation on tumour micro-environment

  • Alina Santiago

      Affiliations

    • Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • OncoRay Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • ,
  • Wolfgang Eicheler

      Affiliations

    • Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • OncoRay Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • Experimental Center, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • ,
  • Jan Bussink

      Affiliations

    • Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    • ,
  • Paul Rijken

      Affiliations

    • Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    • ,
  • Ala Yaromina

      Affiliations

    • Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • OncoRay Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • ,
  • Bettina Beuthien-Baumann

      Affiliations

    • Department of Nuclear Medicine, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • ,
  • Albert J. van der Kogel

      Affiliations

    • Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    • ,
  • Michael Baumann

      Affiliations

    • Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • OncoRay Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • Experimental Center, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • ,
  • Mechthild Krause

      Affiliations

    • Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • OncoRay Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
    • Corresponding Author InformationCorresponding author. Address: Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.

Received 7 February 2010 ,Revised 4 July 2010 ,Accepted 7 July 2010.

References 

  1. Zimmermann M, Zouhair A, Azria D, Ozsahin M. The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications. Radiat Oncol. 2006;1:11
  2. Baumann M, Krause M. Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results. Radiother Oncol. 2004;72:257–266
  3. Baumann M, Krause M, Dikomey E, et al. EGFR-targeted anti-cancer drugs in radiotherapy: preclinical evaluation of mechanisms. Radiother Oncol. 2007;83:238–248
  4. Dittmann K, Mayer C, Kehlbach R, Rothmund MC, Peter Rodemann H. Radiation-induced lipid peroxidation activates src kinase and triggers nuclear EGFR transport. Radiother Oncol. 2009;92:379–382
  5. Rodemann HP, Dittmann K, Toulany M. Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol. 2007;83:781–791
  6. Dittmann K, Mayer C, Fehrenbacher B, et al. Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. J Biol Chem. 2005;280:31182–31189
  7. Bandyopadhyay D, Mandal M, Adam L, Mendelsohn J, Kumar R. Physical interaction between epidermal growth factor receptor and DNA-dependent protein kinase in mammalian cells. J Biol Chem. 1998;273:1568–1573
  8. Lo HW, Hung MC. Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival. Br J Cancer. 2006;94:184–188
  9. Wanner G, Mayer C, Kehlbach R, Rodemann HP, Dittmann K. Activation of protein kinase Cepsilon stimulates DNA-repair via epidermal growth factor receptor nuclear accumulation. Radiother Oncol. 2008;86:383–390
  10. Meyn RE, Munshi A, Haymach JV, Milas L, Ang KK. Receptor signaling as a regulatory mechanism of DNA repair. Radiother Oncol. 2009;92:316–322
  11. Lin SY, Makino K, Xia W, et al. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol. 2001;3:802–808
  12. Waugh MG, Hsuan JJ. EGF receptors as transcription factors: ridiculous or sublime?. Nat Cell Biol. 2001;3:E209–211
  13. Schmidt-Ullrich RK, Valerie K, Fogleman PB, Walters J. Radiation-induced autophosphorylation of epidermal growth factor receptor in human malignant mammary and squamous epithelial cells. Radiat Res. 1996;145:81–85
  14. Dent P, Reardon DB, Park JS, et al. Radiation-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. 1999;10:2493–2506
  15. Petersen C, Eicheler W, Frommel A, et al. Proliferation and micromilieu during fractionated irradiation of human FaDu squamous cell carcinoma in nude mice. Int J Radiat Biol. 2003;79:469–477
  16. Petersen C, Zips D, Krause M, et al. Repopulation of FaDu human squamous cell carcinoma during fractionated radiotherapy correlates with reoxygenation. Int J Radiat Oncol Biol Phys. 2001;51:483–493
  17. Thomas SM, Grandis JR. Pharmacokinetic and pharmacodynamic properties of EGFR inhibitors under clinical investigation. Cancer Treat Rev. 2004;30:255–268
  18. Dittmann K, Mayer C, Rodemann HP. Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity. Radiother Oncol. 2005;76:157–161
  19. Huang SM, Harari PM. Modulation 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. 2000;6:2166–2174
  20. Nasu S, Ang KK, Fan Z, Milas L. C225 antiepidermal growth factor receptor antibody enhances tumor radiocurability. Int J Radiat Oncol Biol Phys. 2001;51:474–477
  21. Milas L, Fang FM, Mason KA, et al. Importance of maintenance therapy in C225-induced enhancement of tumor control by fractionated radiation. Int J Radiat Oncol Biol Phys. 2007;67:568–572
  22. Krause M, Schutze C, Petersen C, et al. Different classes of EGFR inhibitors may have different potential to improve local tumour control after fractionated irradiation: a study on C225 in FaDu hSCC. Radiother Oncol. 2005;74:109–115
  23. Krause M, Ostermann G, Petersen C, et al. Decreased repopulation as well as increased reoxygenation contribute to the improvement in local control after targeting of the EGFR by C225 during fractionated irradiation. Radiother Oncol. 2005;76:162–167
  24. Krause M, Baumann M. Clinical biomarkers of kinase activity: examples from EGFR inhibition trials. Cancer Metastasis Rev. 2008;27:387–402
  25. Krause M, Gurtner K, Deuse Y, Baumann M. Heterogeneity of tumour response to combined radiotherapy and EGFR inhibitors: Differences between antibodies and TK inhibitors. Int J Radiat Biol. 2010;85:943–954
  26. Riesterer O, Mason KA, Raju U, et al. Enhanced response to C225 of A431 tumor xenografts growing in irradiated tumor bed. Radiother Oncol. 2009;92:383–387
  27. Eicheler W, Zips D, Dorfler A, Grenman R, Baumann M. Splicing mutations in TP53 in human squamous cell carcinoma lines influence immunohistochemical detection. J Histochem Cytochem. 2002;50:197–204
  28. Zietman AL, Suit HD, Ramsay JR, Silobrcic V, Sedlacek RS. Quantitative studies on the transplantability of murine and human tumors into the brain and subcutaneous tissues of NCr/Sed nude mice. Cancer Res. 1988;48:6510–6516
  29. Bentzen SM, Atasoy BM, Daley FM, et al. Epidermal 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. 2005;23:5560–5567
  30. Sebastian S, Settleman J, Reshkin SJ, Azzariti A, Bellizzi A, Paradiso A. The complexity of targeting EGFR signalling in cancer: From expression to turnover. Biochim Biophys Acta. 2006;1766:120–139
  31. Sunada H, Magun BE, Mendelsohn J, MacLeod CL. Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation. Proc Natl Acad Sci USA. 1986;83:3825–3829
  32. Fan Z, Mendelsohn J, Masui H, Kumar R. Regulation of epidermal growth factor receptor in NIH3T3/HER14 cells by antireceptor monoclonal antibodies. J Biol Chem. 1993;268:21073–21079
  33. Yoshida T, Okamoto I, Okabe T, et al. Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk. Int J Cancer. 2008;122:1530–1538
  34. Goldkorn T, Balaban N, Shannon M, Matsukuma K. EGF receptor phosphorylation is affected by ionizing radiation. Biochim Biophys Acta. 1997;1358:289–299
  35. Sturla LM, Amorino G, Alexander MS, Mikkelsen RB, Valerie K, Schmidt-Ullrichr RK. Requirement of Tyr-992 and Tyr-1173 in phosphorylation of the epidermal growth factor receptor by ionizing radiation and modulation by SHP2. J Biol Chem. 2005;280:14597–14604
  36. Baumann M, Krause M, Zips D, et al. Selective inhibition of the epidermal growth factor receptor tyrosine kinase by BIBX1382BS and the improvement of growth delay, but not local control, after fractionated irradiation in human FaDu squamous cell carcinoma in the nude mouse. Int J Radiat Biol. 2003;79:547–559
  37. Mukohara T, Engelman JA, Hanna NH, et al. Differential effects of gefitinib and cetuximab on non-small-cell lung cancers bearing epidermal growth factor receptor mutations. J Natl Cancer Inst. 2005;97:1185–1194
  38. Feng FY, Lopez CA, Normolle DP, et al. Effect of epidermal growth factor receptor inhibitor class in the treatment of head and neck cancer with concurrent radiochemotherapy in vivo. Clin Cancer Res. 2007;13:2512–2518
  39. Toulany M, Kehlbach R, Florczak U, et al. Targeting of AKT1 enhances radiation toxicity of human tumor cells by inhibiting DNA-PKcs-dependent DNA double-strand break repair. Mol Cancer Ther. 2008;7:1772–1781
  40. Toulany M, Baumann M, Rodemann HP. Stimulated PI3K-AKT signaling mediated through ligand or radiation-induced EGFR depends indirectly, but not directly, on constitutive K-Ras activity. Mol Cancer Res. 2007;5:863–872
  41. Masui H, Kawamoto T, Sato JD, Wolf B, Sato G, Mendelsohn J. Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res. 1984;44:1002–1007
  42. Bier H, Reiffen KA, Haas I, Stasiecki P. Dose-dependent access of murine anti-epidermal growth factor receptor monoclonal antibody to tumor cells in patients with advanced laryngeal and hypopharyngeal carcinoma. Eur Arch Otorhinolaryngol. 1995;252:433–439

PII: S0167-8140(10)00395-6

doi: 10.1016/j.radonc.2010.07.007

Radiotherapy & Oncology
Volume 97, Issue 2 , Pages 322-329 , November 2010

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