Molecular biomarkers for prognosis and optimal treatment strategy of glioblastomas

L. A. Dzyak, N. A. Zorin, A. G. Sirko, V. I. Shpohnka, A. V. Kozinskiy


An overview of recent publications, dedicated to molecular biomarkers role in prognosis and optimal treatment strategy of glioblastomas, based on targeted therapy approach, is presented. The emphasis is made on those biomarkers that were extensively studied. Also clinical trials data, in which various glioblastoma treatment regimens were studied, are given.


глиобластома; иммуногистохимические методы; таргетная терапия; темозоломид; MGMT; EGFR; PTEN


Зозуля Ю.А., Сенько Л.Н. Молекулярные механизмы онкогенеза глиом головного мозга // Укр. нейрохірург. журн. — 2000. — №1. — С.6–15.

Кобяков Г.Л., Борисов В.И., Абсалямова О.В. и др. Химиолучевая терапия с темозоломидом больных глиобластомой // Фарматека. — 2008. — №18. — С.67–72.

Лисяный Н.И., Семенова В.М., Любич Л.Д. Достижения и проблемы применения интерферонов в нейроонкологии // Укр. нейрохірург. журн. — 2004. — №3. — С.29–37.

Розуменко В.Д., Главацкий О.Я., Васильева И.Г. и др. Основные фенотипические проявления и принципы формирования генотипа злокачественных опухолей головного мозга // Укр. нейрохірург. журн. — 2004. — №3. — С.4–14.

Adamson C., Kanu O.O., Mehta A.I. et al. Glioblastoma multiforme: a review of where we have been and where we are going // Expert Opin. Invest. Drugs. — 2009. — V.18. — P.1061–1083.

Anda T., Shabani H.K., Tsunoda K. et al. Relationship between expression of O6-methylguanine-DNA methyltransferase, glutathione-S-transferase in glioblastoma and the survival of the patients treated with nimustine hydrochloride: an immunohistochemical analysis // Neurol. Res. — 2003. — V.25. — P.241–248.

Aoki T., Hashimoto N., Matsutani M. Management of glioblastoma // Expert Opin. Pharmacother. — 2007. — V.8. — P.3133–3146.

Brell M., Tortosa A., Verger E. et al. Prognostic significance of O6-methylguanine-DNA methyltransferase determined by promoter hypermethylation and immunohistochemical expression in anaplastic gliomas // Clin. Cancer Res. — 2005. — V.11. — P.5167–5174.

Brown P.D., Krishnan S., Sarkaria J.N. et al. Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177 // J. Clin. Oncol. — 2008. — V.26. — P.5603–5609.

Chu E.C., Tarnawski A.S. PTEN regulatory functions in tumor suppression and cell biology // Med. Sci. Monit. — 2004. — V.10. — P.235–241.

Costello J.F., Futscher B.W., Tano K. et al. Graded methylation in the promoter and body of the O6-methylguanine DNA methyltransferase (MGMT) gene correlates with MGMT expression in human glioma cells // J. Biol. Chem. — 1994. — V.269. — P.17228–17237.

Crinire E., Kaloshi G., Laigle-Donadey F. et al. MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities // J. Neurooncol. — 2007. — V.83. — P.173–179.

Cutter J.L., Kurozumi K., Chiocca E.A. et al. Gene therapeutics: the future of brain tumor therapy? // Expert Rev. Anticancer Ther. — 2006. — V.6. — P.1053–1064.

Di Leo A., Cardoso F., Durbecq V. et al. Predictive molecular markers in the adjuvant therapy of breast cancer: state of the art in the year 2002 // Int. J. Clin. Oncol. — 2002. — V.7. — P.245–253.

Dunn J., Baborie A., Alam F. et al. Extent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy // Br. J. Cancer. — 2009. — V.7. — P.124–131.

Frenel J.S., Botti M., Loussouarn D. et al. Prognostic and predictive factors for gliomas in adults // Bull. Cancer. — 2009. — V.96. — P.357–367.

Friedman H., Kerby T., Calvert H. Temozolomide and treatment of malignant glioma // Clin. Cancer Res. — 2000. — V.6. — P.2585–2597.

Hegi M.E., Diserens A.C., Gorlia T. et al. MGMT gene silencing and benefit from temozolomide in glioblastoma // New Engl. J. Med. — 2005. — V.352. — P.997–1003.

Herbst R.S. Review of epidermal growth factor receptor biology // Int. J. Radiat. Oncol. Biol. Phys. — 2004. — V.59. — P.21–26.

Herman J.G., Graff J.R., Myhnen S. et al. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands // Proc. Natl. Acad. Sci. USA. — 1996. — V.93. — P.9821–9826.

Korshunov A., Golanov A., Sycheva R. Immunohistochemical markers for prognosis of cerebral glioblastomas // J. Neurooncol. — 2002. — V.58. — P.217–236.

Koukourakis G.V., Kouloulias V., Zacharias G. et al. Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article // Molecules. —2009. — V.14. — P.1561–1577.

Koul D. PTEN signaling pathways in glioblastoma // Cancer Biol. Ther. — 2008. — V.7. — P.1321–1325.

Li L., Dutra A., Pak E., Labrie J.E. 3rd. EGFRvIII expression and PTEN loss synergistically induce chromosomal instability and glial tumors // Neurooncol. — 2009. — V.11. — P.9–21.

Marijnen C.A., van den Berg S.M., van Duinen S.G. et al. Radiotherapy is effective in patients with glioblastoma multiforme with a limited prognosis and in patients above 70 years of age: a retrospective single institution analysis // Radiother. Oncol. — 2005. — V.75. — P.210–216.

Matlashewski G., Lamb P., Pim D. et al. Isolation and characterization of a human p53 cDNA clone: expression of the human p53 gene // EMBO J. — 1984. — V.3. — P.3257–3262.

Nakagawa T., Ido K., Sakuma T. et al. Prognostic significance of the immunohistochemical expression of O6-methylguanine-DNA methyltransferase, P-glycoprotein, and multidrug resistance protein-1 inglioblastomas // Neuropathology. — 2008. — V.29. — P.379–388.

Natsume A., Ishii D., Wakabayashi T. et al. IFN- down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide // Cancer Res. — 2005. — V.65. — P.7573–7579.

Nicholas M.K. Glioblastoma multiforme: evidence-based approach to therapy // Expert Rev. Anticancer Ther. — 2007. — V.7, suppl.12. — P.23–27.

Parvez T. Present trend in the primary treatment of aggressive malignant glioma: glioblastoma multiforme // Technol. Cancer Res. Treat. — 2008. — V.7. — P.241–248.

Prados M.D., Chang S.M., Butowski N. et al. Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma // Clin. Oncol. — 2009. — V.27. — P.579–584.

Preusser M., Janzer C.R., Felsberg J. et al. Anti-O6-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: observer variability and lack of association with patient survival impede its use as clinical biomarker // Brain Pathol. — 2008. — V.18. — P.520–532.

Reavey-Cantwell J.F.,HarounR.I., Zahurak M. The prognostic value of tumor markers in patients with glioblastoma multiforme: analysis of 32 patients and review of the literature // J. Neurooncol. — 2001. — V.55. — P.195–204.

Rodriguez F.J., Thibodeau S.N., Jenkins R.B. et al. MGMT immunohistochemical expression and promoter methylation in human glioblastoma // Appl. Immunohistochem. Mol. Morphol. — 2008. — V.16. — P.59–65.

Rosati S.F., Williams R.F., Nunnally L.C. et al. IFN-beta sensitizes neuroblastoma to the antitumor activity of temozolomide by modulating O6-methylguanine DNA methyltransferase expression // Mol. Cancer Ther. — 2008. — V.7. — P.3852–3858.

Scholzen T., Gerdes J. The Ki-67 protein: from the known and the unknown // J. Cell Physiol. — 2000. — V.182. — P.311–322.

Schwartzbaum J.A., Fisher J.L., Aldape K.D., Wrensch M. Epidemiology and molecular pathology of glioma // Nat. Clin. Pract. Neurol. — 2006. — V.2. — P.494–503.

Selznick L.A., Shamji M.F., Fecci P. et al. Molecular strategies for the treatment of malignant glioma-genes, viruses, and vaccines // Neurosurg. Rev. — 2008. — V.31. — P.141–155.

Stupp R.,GanderM., Leyvraz S. Current and future developments in the use of temozolomide for the treatment of brain tumours // Lancet Oncol. — 2001. — V.2. — P.552–560.

Stupp R.,HegiM.E., Gilbert M.R. et al. Chemoradiotherapy in malignant glioma: standard of care and future directions // J. Clin. Oncol. — 2007. — V.25. — P.4127–4136.

Stupp R., Hegi M.E., Mason W.P. et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial // Lancet Oncol. — 2009. — V.10. — P.459–466.

Voelzke W.R., Petty W.J., Lesser G.J. Targeting the epidermal growth factor receptor in high-grade astrocytomas // Curr. Treat Options Oncol. — 2008. — V.9. — P.23–31.

Wakabayashi T., Kayama T., Nishikawa R. et al. A multicenter phase I trial of interferon-β and temozolomide combination therapy for high-grade gliomas (INTEGRA Study) // Japn. J. Clin. Oncol. — 2008. — V.38. — P.715–718.

Zhu H., Acquaviva J., Ramachandran P. et al. Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in glioma genesis // Proc. Natl. Acad. Sci. USA. — 2009. — V.106. — P.2712–2716.

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