International Journal of Radiation Oncology * Biology * Physics
Volume 75, Issue 1 , Pages 212-219 , 1 September 2009

Radiosensitizing Effects of Temozolomide Observed in vivo only in a Subset of O6-Methylguanine-DNA Methyltransferase Methylated Glioblastoma Multiforme Xenografts

  • Brett L. Carlson, B.S.

      Affiliations

    • Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Patrick T. Grogan, B.S.

      Affiliations

    • Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Ann C. Mladek, B.S.

      Affiliations

    • Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Mark A. Schroeder

      Affiliations

    • Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Gaspar J. Kitange, M.D., Ph.D.

      Affiliations

    • Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Paul A. Decker, M.S.

      Affiliations

    • Department of Biostatistics, Mayo Clinic, Rochester, Minnesota
  • ,
  • Caterina Giannini, M.D.

      Affiliations

    • Department of Pathology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Wenting Wu, Ph.D.

      Affiliations

    • Department of Biostatistics, Mayo Clinic, Rochester, Minnesota
  • ,
  • Karla A. Ballman, Ph.D.

      Affiliations

    • Department of Biostatistics, Mayo Clinic, Rochester, Minnesota
  • ,
  • C. David James, Ph.D.

      Affiliations

    • Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, California
  • ,
  • Jann N. Sarkaria, M.D.

      Affiliations

    • Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
    • Corresponding Author InformationReprint requests to: Jann Sarkaria, M.D., Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Tel.: (507) 266-3877; Fax: (507) 284-0079

Received 16 March 2009 ,Revised 20 April 2009 ,Accepted 22 April 2009.

References 

  1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–996
  2. Hegi ME, Diserens A-C, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003
  3. Paz MF, Yaya-Tur R, Rojas-Marcos I, et al. CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas. Clin Cancer Res. 2004;10:4933–4938
  4. Lawrence TS, Blackstock AW, McGinn C. The mechanism of action of radiosensitization of conventional chemotherapeutic agents. Semin Radiat Oncol. 2003;13:13–21
  5. McGinn CJ, Lawrence TS. Recent advances in the use of radiosensitizing nucleosides. Semin Radiat Oncol. 2001;11:270–280
  6. Byfield JE. 5-Fluorouracil radiation sensitization–-A brief review. Invest New Drugs. 1989;7:111–116
  7. Wedge SR, Porteous JK, Glaser MG, et al. In vitro evaluation of temozolomide combined with X-irradiation. Anticancer Drugs. 1997;8:92–97
  8. van Rijn J, Heimans JJ, van den Berg J, et al. Survival of human glioma cells treated with various combination of temozolomide and X-rays. Int J Radiat Oncol Biol Phys. 2000;47:779–784
  9. Chakravarti A, Erkkinen MG, Nestler U, et al. Temozolomide-mediated radiation enhancement in glioblastoma: A report on underlying mechanisms. Clin Cancer Res. 2006;12:4738–4746
  10. Combs SE, Schulz-Ertner D, Roth W, et al. In vitro responsiveness of glioma cell lines to multimodality treatment with radiotherapy, temozolomide, and epidermal growth factor receptor inhibition with cetuximab. Int J Radiat Oncol Biol Phys. 2007;68:873–882
  11. van Nifterik KA, van den Berg J, Stalpers LJA, et al. Differential radiosensitizing potential of temozolomide in MGMT promoter methylated glioblastoma multiforme cell lines. Int J Radiat Oncol Biol Phys. 2007;69:1246–1253
  12. Kitange GJ, Carlson BL, Schroeder MA, et al. Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts. Neuro-oncol. 2009;92:23–31
  13. Dinca EB, Lu KV, Sarkaria JN, et al. p53 Small-molecule inhibitor enhances temozolomide cytotoxic activity against intracranial glioblastoma xenografts. Cancer Res. 2008;68:10034–10039
  14. Yung WK, Albright RE, Olson J, et al. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000;83:588–593
  15. Brada M, Hoang-Xuan K, Rampling R, et al. Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse. Ann Oncol. 2001;12:259–266
  16. Sarkaria JN, Carlson BL, Schroeder MA, et al. Use of an Orthotopic xenograft model for assessing the effect of epidermal growth factor receptor amplification on glioblastoma radiation response. Clin Cancer Res. 2006;12:2264–2271
  17. Sarkaria JN, Yang L, Grogan PT, et al. Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Mol Cancer Ther. 2007;6:1167–1174
  18. Yang L, Clarke MJ, Carlson BL, et al. PTEN loss does not predict for response to RAD001 (Everolimus) in a glioblastoma orthotopic xenograft test panel. Clin Cancer Res. 2008;14:3993–4001
  19. Esteller M, Hamilton SR, Burger PC, et al. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res. 1999;59:793–797
  20. Esteller M, Garcia-Foncillas J, Andion E, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000;343:1350–1354
  21. James CD, Galanis E, Frederick L, et al. Tumor suppressor gene alterations in malignant gliomas: Histopathological associations and prognostic evaluation. Int J Oncol. 1999;15:547–553
  22. Giannini C, Hebrink D, Scheithauer BW, et al. Analysis of p53 mutation and expression in pleomorphic xanthoastrocytoma. Neurogenetics. 2001;3:159–162
  23. Smith JS, Tachibana I, Passe SM, et al. PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst. 2001;93:1246–1256
  24. Liu W, James CD, Frederick L, et al. PTEN/MMAC1 mutations and EGFR amplification in glioblastomas. Cancer Res. 1997;57:5254–5257
  25. Hegi ME, Diserens A-C, Godard S, et al. Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res. 2004;10:1871–1874
  26. Stevens MF, Hickman JA, Langdon SP, et al. Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045; M & B 39831), a novel drug with potential as an alternative to dacarbazine. Cancer Res. 1987;47:5846–5852
  27. Baker SD, Wirth M, Statkevich P, et al. Absorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancer. Clin Cancer Res. 1999;5:309–317
  28. Reid JM, Stevens DC, Rubin J, et al. Pharmacokinetics of 3-methyl-(triazen-1-yl)imidazole-4-carboximide following administration of temozolomide to patients with advanced cancer. Clin Cancer Res. 1997;3:2393–2398
  29. Giannini C, Sarkaria J, Saito A, et al. Patient Tumor EGFR and PDGFRA gene amplifications retained in an invasive intracranial xenograft model of GBM. Neuro-oncol. 2005;7:164–176
  30. Pandita A, Aldape KD, Zadeh G, et al. Contrasting in vivo and in vitro fates of glioblastoma cell subpopulations with amplified EGFR. Genes Chromosomes Cancer. 2004;39:29–36
  31. Jackson PE, Cooper DP, Meyer TA, et al. Formation and persistence of O(6)-methylguanine in the mouse colon following treatment with 1,2-dimethylhydrazine as measured by an O(6)-alkylguanine-DNA alkyltransferase inactivation assay. Toxicol Lett. 2000;115:205–212
  32. O'Connor PJ, Manning FC, Gordon AT, et al. DNA repair: kinetics and thresholds. Toxicol Pathol. 2000;28:375–381

 This work was supported by the Mayo Foundation, the National Cancer Institute (CA108961 and CA127716), and the Brain Tumor Funders Consortium.

 Conflict of interest: none.

PII: S0360-3016(09)00603-8

doi: 10.1016/j.ijrobp.2009.04.026

International Journal of Radiation Oncology * Biology * Physics
Volume 75, Issue 1 , Pages 212-219 , 1 September 2009