Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2017, Article ID 8013575, 13 pages
https://doi.org/10.1155/2017/8013575
Review Article

Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives

1Department of Neurosurgery, Medical University of Silesia, Regional Hospital, Sosnowiec, Poland
2Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK

Correspondence should be addressed to Wojciech Kaspera; lp.ude.mus@arepsakw

Received 11 August 2016; Accepted 13 December 2016; Published 20 February 2017

Academic Editor: Franco M. Buonaguro

Copyright © 2017 Wojciech Szopa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Q. T. Ostrom, P. M. De Blank, C. Kruchko et al., “Alex's Lemonade stand foundation infant and childhood primary brain and central nervous system tumors diagnosed in the United States in 2007–2011,” Neuro-Oncology, vol. 16, supplement 10, pp. x1–x36, 2015. View at Publisher · View at Google Scholar · View at Scopus
  2. M. L. Affronti, C. R. Heery, J. E. Herndon II et al., “Overall survival of newly diagnosed glioblastoma patients receiving carmustine wafers followed by radiation and concurrent temozolomide plus rotational multiagent chemotherapy,” Cancer, vol. 115, no. 15, pp. 3501–3511, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. B. J. Theeler and M. R. Gilbert, “Advances in the treatment of newly diagnosed glioblastoma,” BMC Medicine, vol. 13, article 293, 2015. View at Publisher · View at Google Scholar · View at Scopus
  4. W. Taal, H. M. Oosterkamp, A. M. E. Walenkamp et al., “Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial,” The Lancet Oncology, vol. 15, no. 9, pp. 943–953, 2014. View at Publisher · View at Google Scholar · View at Scopus
  5. K. Aldape, G. Zadeh, S. Mansouri, G. Reifenberger, and A. von Deimling, “Glioblastoma: pathology, molecular mechanisms and markers,” Acta Neuropathologica, vol. 129, no. 6, article 1432, pp. 829–848, 2015. View at Publisher · View at Google Scholar · View at Scopus
  6. S. K. Carlsson, S. P. Brothers, and C. Wahlestedt, “Emerging treatment strategies for glioblastoma multiforme,” EMBO Molecular Medicine, vol. 6, no. 11, pp. 1359–1370, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. D. N. Louis, H. Ohgaki, O. D. Wiestler et al., “The 2007 WHO classification of tumours of the central nervous system,” Acta Neuropathologica, vol. 114, no. 2, pp. 97–109, 2007. View at Publisher · View at Google Scholar
  8. D. N. Louis, A. Perry, G. Reifenberger et al., “The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary,” Acta Neuropathologica, vol. 131, no. 6, pp. 803–820, 2016. View at Publisher · View at Google Scholar · View at Scopus
  9. H. Ohgaki and P. Kleihues, “The definition of primary and secondary glioblastoma,” Clinical Cancer Research, vol. 19, no. 4, pp. 764–772, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Ohgaki, P. Dessen, B. Jourde et al., “Genetic pathways to glioblastoma: a population-based study,” Cancer Research, vol. 64, no. 19, pp. 6892–6899, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Nakamura, T. Watanabe, Y. Yonekawa, P. Kleihues, and H. Ohgaki, “Promoter methylation of the DNA repair gene MGMT in astrocytomas is frequently associated with G:C → A:T mutations of the TP53 tumor suppressor gene,” Carcinogenesis, vol. 22, no. 10, pp. 1715–1719, 2001. View at Publisher · View at Google Scholar · View at Scopus
  12. H. Yan, D. W. Parsons, G. Jin et al., “IDH1 and IDH2 mutations in gliomas,” New England Journal of Medicine, vol. 360, no. 8, pp. 765–773, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. H. S. Phillips, S. Kharbanda, R. Chen et al., “Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis,” Cancer Cell, vol. 9, no. 3, pp. 157–173, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. R. G. W. Verhaak, K. A. Hoadley, E. Purdom et al., “Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1,” Cancer Cell, vol. 17, no. 1, pp. 98–110, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. C. W. Brennan, R. G. Verhaak, A. McKenna et al., “The somatic genomic landscape of glioblastoma,” Cell, vol. 155, no. 2, pp. 462–477, 2013. View at Google Scholar
  16. J. Wang, H.-K. Su, H.-F. Zhao, Z.-P. Chen, and S.-S. T. To, “Progress in the application of molecular biomarkers in gliomas,” Biochemical and Biophysical Research Communications, vol. 465, no. 1, pp. 1–4, 2015. View at Publisher · View at Google Scholar · View at Scopus
  17. J. T. Huse and E. C. Holland, “Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma,” Nature Reviews Cancer, vol. 10, no. 5, pp. 319–331, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. A. Sottoriva, I. Spiteri, S. G. M. Piccirillo et al., “Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 10, pp. 4009–4014, 2013. View at Publisher · View at Google Scholar · View at Scopus
  19. T. R. Jue and K. L. McDonald, “The challenges associated with molecular targeted therapies for glioblastoma,” Journal of Neuro-Oncology, vol. 127, no. 3, pp. 427–434, 2016. View at Publisher · View at Google Scholar · View at Scopus
  20. G. Farias-Eisner, A. M. Bank, B. Y. Hwang et al., “Glioblastoma biomarkers from bench to bedside: advances and challenges,” British Journal of Neurosurgery, vol. 26, no. 2, pp. 189–194, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. K. P. L. Bhat, V. Balasubramaniyan, B. Vaillant et al., “Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma,” Cancer Cell, vol. 24, no. 3, pp. 331–346, 2013. View at Publisher · View at Google Scholar · View at Scopus
  22. P. Mao, K. Joshi, J. Li et al., “Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 21, pp. 8644–8649, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. I. Nakano, “Stem cell signature in glioblastoma: therapeutic development for a moving target,” Journal of Neurosurgery, vol. 122, no. 2, pp. 324–330, 2015. View at Publisher · View at Google Scholar · View at Scopus
  24. R. Chakrabarti, J. Hwang, M. Andres Blanco et al., “Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2,” Nature Cell Biology, vol. 14, no. 11, pp. 1212–1222, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. D. J. Aum, D. H. Kim, T. L. Beaumont, E. C. Leuthardt, G. P. Dunn, and A. H. Kim, “Molecular and cellular heterogeneity: the hallmark of glioblastoma,” Neurosurgical Focus, vol. 37, no. 6, article E11, 2014. View at Publisher · View at Google Scholar · View at Scopus
  26. P. Y. Wen and S. Kesari, “Malignant gliomas in adults,” New England Journal of Medicine, vol. 359, no. 5, pp. 492–507, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. F. B. Furnari, T. Fenton, R. M. Bachoo et al., “Malignant astrocytic glioma: genetics, biology, and paths to treatment,” Genes and Development, vol. 21, no. 21, pp. 2683–2710, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. H. Ohgaki and P. Kleihues, “Genetic alterations and signaling pathways in the evolution of gliomas,” Cancer Science, vol. 100, no. 12, pp. 2235–2241, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. I. K. Mellinghoff, M. Y. Wang, I. Vivanco et al., “Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors,” The New England Journal of Medicine, vol. 353, no. 19, pp. 2012–2024, 2005. View at Google Scholar
  30. E. Padfield, H. P. Ellis, and K. M. Kurian, “Current therapeutic advances targeting EGFR and EGFRvIII in glioblastoma,” Frontiers in Oncology, vol. 5, article no. 5, 2015. View at Publisher · View at Google Scholar
  31. F. B. Furnari, T. F. Cloughesy, W. K. Cavenee, and P. S. Mischel, “Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma,” Nature Reviews Cancer, vol. 15, no. 5, pp. 302–310, 2015. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Hobbs, M. N. Nikiforova, D. W. Fardo et al., “Paradoxical relationship between the degree of EGFR amplification and outcome in glioblastomas,” The American Journal of Surgical Pathology, vol. 36, no. 8, pp. 1186–1193, 2012. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Weller, K. Kaulich, B. Hentschel et al., “Assessment and prognostic significance of the epidermal growth factor receptor vIII mutation in glioblastoma patients treated with concurrent and adjuvant temozolomide radiochemotherapy,” International Journal of Cancer, vol. 134, no. 10, pp. 2437–2447, 2014. View at Publisher · View at Google Scholar · View at Scopus
  34. C. E. Pelloski, K. V. Ballman, A. F. Furth et al., “Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma,” Journal of Clinical Oncology, vol. 25, no. 16, pp. 2288–2294, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Faulkner, A. Palmer, H. Williams et al., “EGFR and EGFRvIII analysis in glioblastoma as therapeutic biomarkers,” British Journal of Neurosurgery, vol. 29, no. 1, pp. 23–29, 2015. View at Publisher · View at Google Scholar · View at Scopus
  36. A. B. Heimberger, R. Hlatky, D. Suki et al., “Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients,” Clinical Cancer Research, vol. 11, no. 4, pp. 1462–1466, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. D. A. Haas-Kogan, M. D. Prados, T. Tihan et al., “Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib,” Journal of the National Cancer Institute, vol. 97, no. 12, pp. 880–887, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. A. M. P. Omuro, S. Faivre, and E. Raymond, “Lessons learned in the development of targeted therapy for malignant gliomas,” Molecular Cancer Therapeutics, vol. 6, no. 7, pp. 1909–1919, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. E. Franceschi, G. Cavallo, S. Lonardi et al., “Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO),” British Journal of Cancer, vol. 96, no. 7, pp. 1047–1051, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. C. Alifieris and D. T. Trafalis, “Glioblastoma multiforme: pathogenesis and treatment,” Pharmacology and Therapeutics, vol. 152, pp. 63–82, 2015. View at Publisher · View at Google Scholar · View at Scopus
  41. S. Sathornsumetee, D. A. Reardon, A. Desjardins, J. A. Quinn, J. J. Vredenburgh, and J. N. Rich, “Molecularly targeted therapy for malignant glioma,” Cancer, vol. 110, no. 1, pp. 13–24, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. C. A. Del Vecchio, C. P. Giacomini, H. Vogel et al., “EGFRvIII gene rearrangement is an early event in glioblastoma tumorigenesis and expression defines a hierarchy modulated by epigenetic mechanisms,” Oncogene, vol. 32, no. 21, pp. 2670–2681, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. N. Shinojima, K. Tada, S. Shiraishi et al., “Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme,” Cancer Research, vol. 63, no. 20, pp. 6962–6970, 2003. View at Google Scholar · View at Scopus
  44. N. Montano, T. Cenci, M. Martini et al., “Expression of EGFRvIII in glioblastoma: prognostic significance revisited,” Neoplasia, vol. 13, no. 12, pp. 1113–1121, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. R. Chen, A. L. Cohen, and H. Colman, “Targeted therapeutics in patients with high-grade gliomas: past, present, and future,” Current Treatment Options in Oncology, vol. 17, no. 8, article no. 42, 2016. View at Publisher · View at Google Scholar · View at Scopus
  46. X. Li, C. Wu, N. Chen et al., “PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma,” Oncotarget, vol. 7, no. 22, pp. 33440–33450, 2016. View at Publisher · View at Google Scholar · View at Scopus
  47. A. Sami and M. Karsy, “Targeting the PI3K/AKT/mTOR signaling pathway in glioblastoma: novel therapeutic agents and advances in understanding,” Tumor Biology, vol. 34, no. 4, pp. 1991–2002, 2013. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Nakada, D. Kita, T. Watanabe et al., “Aberrant signaling pathways in Glioma,” Cancers, vol. 3, no. 3, pp. 3242–3278, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. D. A. Reardon, G. Dresemann, S. Taillibert et al., “Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma,” British Journal of Cancer, vol. 101, no. 12, pp. 1995–2004, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. D. Singh, J. M. Chan, P. Zoppoli et al., “Transforming fusions of FGFR and TACC genes in human glioblastoma,” Science, vol. 337, no. 6099, pp. 1231–1235, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Abounader and J. Laterra, “Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis,” Neuro-Oncology, vol. 7, no. 4, pp. 436–451, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. J. T. Huse and K. D. Aldape, “The evolving role of molecular markers in the diagnosis and management of diffuse glioma,” Clinical Cancer Research, vol. 20, no. 22, pp. 5601–5611, 2014. View at Publisher · View at Google Scholar · View at Scopus
  53. Cancer Genome Atlas Research Network, “Comprehensive genomic characterization defines human glioblastoma genes and core pathways,” Nature, vol. 455, no. 7216, pp. 1061–1068, 2008. View at Google Scholar
  54. A. Joy, A. Ramesh, I. Smirnov et al., “AKT pathway genes define 5 prognostic subgroups in glioblastoma,” PLoS ONE, vol. 9, no. 7, Article ID e100827, 2014. View at Publisher · View at Google Scholar · View at Scopus
  55. D. W. Parsons, S. Jones, X. Zhang et al., “An integrated genomic analysis of human glioblastoma multiforme,” Science, vol. 321, no. 5897, pp. 1807–1812, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. K. H. Vousden and D. P. Lane, “p53 in health and disease,” Nature Reviews Molecular Cell Biology, vol. 8, no. 4, pp. 275–283, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. O. Bögler, H.-J. S. Huang, P. Kleihues, and W. K. Cavenee, “The p53 gene and its role in human brain tumors,” Glia, vol. 15, no. 3, pp. 308–327, 1995. View at Publisher · View at Google Scholar · View at Scopus
  58. C. Gomez-Manzano, J. Fueyo, A. P. Kyritsis et al., “Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis,” Cancer Research, vol. 56, no. 4, pp. 694–699, 1996. View at Google Scholar · View at Scopus
  59. H. Ohgaki and P. Kleihues, “Genetic pathways to primary and secondary glioblastoma,” American Journal of Pathology, vol. 170, no. 5, pp. 1445–1453, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. F. J. Stott, S. Bates, M. C. James et al., “The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2,” EMBO Journal, vol. 17, no. 17, pp. 5001–5014, 1998. View at Publisher · View at Google Scholar · View at Scopus
  61. C. J. Sherr and J. M. Roberts, “CDK inhibitors: positive and negative regulators of G1-phase progression,” Genes and Development, vol. 13, no. 12, pp. 1501–1512, 1999. View at Publisher · View at Google Scholar · View at Scopus
  62. C. L. Appin and D. J. Brat, “Molecular pathways in gliomagenesis and their relevance to neuropathologic diagnosis,” Advances in Anatomic Pathology, vol. 22, no. 1, pp. 50–58, 2015. View at Publisher · View at Google Scholar · View at Scopus
  63. M. N. T. Thuy, J. K. T. Kam, G. C. Y. Lee et al., “A novel literature-based approach to identify genetic and molecular predictors of survival in glioblastoma multiforme: analysis of 14,678 patients using systematic review and meta-analytical tools,” Journal of Clinical Neuroscience, vol. 22, no. 5, pp. 785–799, 2015. View at Publisher · View at Google Scholar · View at Scopus
  64. X. Xu, J. Zhao, Z. Xu et al., “Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity,” Journal of Biological Chemistry, vol. 279, no. 32, pp. 33946–33957, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. Z. J. Reitman and H. Yan, “Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism,” Journal of the National Cancer Institute, vol. 102, no. 13, pp. 932–941, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. L. Dang, D. W. White, S. Gross et al., “Cancer-associated IDH1 mutations produce 2-hydroxyglutarate,” Nature, vol. 462, no. 7274, pp. 739–744, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. W. Xu, H. Yang, Y. Liu et al., “Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases,” Cancer Cell, vol. 19, no. 1, pp. 17–30, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. N. K. Kloosterhof, L. B. Bralten, H. J. Dubbink, P. J. French, and M. J. van den Bent, “Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma?” The Lancet Oncology, vol. 12, no. 1, pp. 83–91, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. S. Zhao, Y. Lin, W. Xu et al., “Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1α,” Science, vol. 324, no. 5924, pp. 261–265, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Nobusawa, T. Watanabe, P. Kleihues, and H. Ohgaki, “IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas,” Clinical Cancer Research, vol. 15, no. 19, pp. 6002–6007, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. K. Ichimura, D. M. Pearson, S. Kocialkowski et al., “IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas,” Neuro-Oncology, vol. 11, no. 4, pp. 341–347, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. C. G. Duncan, B. G. Barwick, G. Jin et al., “A heterozygous IDH1R132H/WT mutation induces genome-wide alterations in DNA methylation,” Genome Research, vol. 22, no. 12, pp. 2339–2355, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. H. Noushmehr, D. J. Weisenberger, K. Diefes et al., “Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma,” Cancer Cell, vol. 17, no. 5, pp. 510–522, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Turcan, D. Rohle, A. Goenka et al., “IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype,” Nature, vol. 483, no. 7390, pp. 479–483, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Nakamura, Y. Yonekawa, P. Kleihues, and H. Ohgaki, “Promoter hypermethylation of the RB1 gene in glioblastomas,” Laboratory Investigation, vol. 81, no. 1, pp. 77–82, 2001. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Weller, S. M. Pfister, W. Wick, M. E. Hegi, G. Reifenberger, and R. Stupp, “Molecular neuro-oncology in clinical practice: a new horizon,” The Lancet Oncology, vol. 14, no. 9, pp. e370–e379, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Beiko, D. Suki, K. R. Hess et al., “IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection,” Neuro-Oncology, vol. 16, no. 1, pp. 81–91, 2014. View at Publisher · View at Google Scholar · View at Scopus
  78. J.-R. Chen, Y. Yao, H.-Z. Xu, and Z.-Y. Qin, “Isocitrate dehydrogenase (IDH)1/2 mutations as prognostic markers in patients with glioblastomas,” Medicine (Baltimore), vol. 95, no. 9, Article ID e2583, 2016. View at Publisher · View at Google Scholar · View at Scopus
  79. D. Rohle, J. Popovici-Muller, N. Palaskas et al., “An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells,” Science, vol. 340, no. 6132, pp. 626–630, 2013. View at Publisher · View at Google Scholar · View at Scopus
  80. Y.-S. Keum and B. Y. Choi, “Isocitrate dehydrogenase mutations: new opportunities for translational research,” BMB Reports, vol. 48, no. 5, pp. 266–270, 2015. View at Publisher · View at Google Scholar · View at Scopus
  81. F. Wang, J. Travins, B. DeLaBarre et al., “Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation,” Science, vol. 340, no. 6132, pp. 622–626, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Popovici-Muller, J. O. Saunders, F. G. Salituro et al., “Discovery of the first potent inhibitors of mutant IDH1 that lower tumor 2-HG in vivo,” ACS Medicinal Chemistry Letters, vol. 3, no. 10, pp. 850–855, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. M. E. Hegi, A.-C. Diserens, T. Gorlia et al., “MGMT gene silencing and benefit from temozolomide in glioblastoma,” New England Journal of Medicine, vol. 352, no. 10, pp. 997–1003, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. I. Zawlik, S. Vaccarella, D. Kita, M. Mittelbronn, S. Franceschi, and H. Ohgaki, “Promoter methylation and polymorphisms of the MGMT gene in glioblastomas: a population-based study,” Neuroepidemiology, vol. 32, no. 1, pp. 21–29, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Esteller, J. Garcia-Foncillas, E. Andion et al., “Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents,” The New England Journal of Medicine, vol. 343, no. 19, pp. 1350–1354, 2000. View at Publisher · View at Google Scholar
  86. M. F. Paz, R. Yaya-Tur, I. Rojas-Marcos et al., “CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas,” Clinical Cancer Research, vol. 10, no. 15, pp. 4933–4938, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. M. Cominelli, S. Grisanti, S. Mazzoleni et al., “EGFR amplified and overexpressing glioblastomas and association with better response to adjuvant metronomic temozolomide,” Journal of the National Cancer Institute, vol. 107, no. 5, Article ID djv041, 2015. View at Publisher · View at Google Scholar · View at Scopus
  88. W. Wick, M. Platten, C. Meisner et al., “Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial,” The Lancet Oncology, vol. 13, no. 7, pp. 707–715, 2012. View at Publisher · View at Google Scholar · View at Scopus
  89. G. Reifenberger, B. Hentschel, J. Felsberg et al., “Predictive impact of MGMT promoter methylation in glioblastoma of the elderly,” International Journal of Cancer, vol. 131, no. 6, pp. 1342–1350, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. A. Malmström, B. H. Grønberg, C. Marosi et al., “Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial,” The Lancet Oncology, vol. 13, no. 9, pp. 916–926, 2012. View at Publisher · View at Google Scholar · View at Scopus
  91. T. S. Armstrong, J. S. Wefel, M. Wang et al., “Net clinical benefit analysis of radiation therapy oncology group 0525: a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma,” Journal of Clinical Oncology, vol. 31, no. 32, pp. 4076–4084, 2013. View at Publisher · View at Google Scholar · View at Scopus
  92. B. Wiestler, R. Claus, S. A. Hartlieb et al., “Malignant astrocytomas of elderly patients lack favorable molecular markers: an analysis of the NOA-08 study collective,” Neuro-Oncology, vol. 15, no. 8, pp. 1017–1026, 2013. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Weller, G. Tabatabai, B. Kästner et al., “MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive Glioblastoma: the DIRECTOR Trial,” Clinical Cancer Research, vol. 21, no. 9, pp. 2057–2064, 2015. View at Publisher · View at Google Scholar · View at Scopus
  94. B. D. Liebelt, T. Shingu, X. Zhou, J. Ren, S. A. Shin, and J. Hu, “Glioma stem cells: signaling, microenvironment, and therapy,” Stem Cells International, vol. 2016, Article ID 7849890, 10 pages, 2016. View at Publisher · View at Google Scholar · View at Scopus
  95. M. F. Krummel and J. P. Allison, “CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells,” Journal of Experimental Medicine, vol. 183, no. 6, pp. 2533–2540, 1996. View at Publisher · View at Google Scholar · View at Scopus
  96. A. K. S. Salama and F. S. Hodi, “Cytotoxic T-lymphocyte-associated antigen-4,” Clinical Cancer Research, vol. 17, no. 14, pp. 4622–4628, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. O. Bloch, C. A. Crane, R. Kaur, M. Safaee, M. J. Rutkowski, and A. T. Parsa, “Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages,” Clinical Cancer Research, vol. 19, no. 12, pp. 3165–3175, 2013. View at Publisher · View at Google Scholar · View at Scopus
  98. A. T. Parsa, J. S. Waldron, A. Panner et al., “Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma,” Nature Medicine, vol. 13, no. 1, pp. 84–88, 2007. View at Publisher · View at Google Scholar · View at Scopus
  99. T. Doucette, G. Rao, A. Rao et al., “Immune heterogeneity of glioblastoma subtypes: extrapolation from the cancer genome atlas,” Cancer Immunology Research, vol. 1, no. 2, pp. 112–122, 2013. View at Publisher · View at Google Scholar · View at Scopus
  100. A. S. Berghoff, B. Kiesel, G. Widhalm et al., “Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma,” Neuro-Oncology, vol. 17, no. 8, pp. 1064–1075, 2015. View at Publisher · View at Google Scholar · View at Scopus
  101. Y. Liu, R. Carlsson, M. Ambjørn et al., “PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients,” The Journal of Neuroscience, vol. 33, no. 35, pp. 14231–14245, 2013. View at Publisher · View at Google Scholar · View at Scopus
  102. E. K. Nduom, J. Wei, N. K. Yaghi et al., “PD-L1 expression and prognostic impact in glioblastoma,” Neuro-Oncology, vol. 18, no. 2, pp. 195–205, 2016. View at Publisher · View at Google Scholar · View at Scopus
  103. C. Robert, G. V. Long, B. Brady et al., “Nivolumab in previously untreated melanoma without BRAF mutation,” The New England Journal of Medicine, vol. 372, no. 4, pp. 320–330, 2015. View at Publisher · View at Google Scholar · View at Scopus
  104. C. Robert, L. Thomas, I. Bondarenko et al., “Ipilimumab plus dacarbazine for previously untreated metastatic melanoma,” The New England Journal of Medicine, vol. 364, no. 26, pp. 2517–2526, 2011. View at Publisher · View at Google Scholar · View at Scopus
  105. F. S. Hodi, S. J. O'Day, D. F. McDermott et al., “Improved survival with ipilimumab in patients with metastatic melanoma,” New England Journal of Medicine, vol. 363, no. 8, pp. 711–723, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. N. K. Gerber, R. J. Young, C. A. Barker et al., “Ipilimumab and whole brain radiation therapy for melanoma brain metastases,” Journal of Neuro-Oncology, vol. 121, no. 1, pp. 159–165, 2015. View at Publisher · View at Google Scholar · View at Scopus
  107. S. Tanaka, D. N. Louis, W. T. Curry, T. T. Batchelor, and J. Dietrich, “Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end?” Nature Reviews Clinical Oncology, vol. 10, no. 1, pp. 14–26, 2013. View at Publisher · View at Google Scholar · View at Scopus
  108. B. Fong, R. Jin, X. Wang et al., “Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients,” PLoS ONE, vol. 7, no. 4, Article ID e32614, 2012. View at Publisher · View at Google Scholar · View at Scopus
  109. R. F. Barajas Jr., J. S. Chang, M. R. Segal et al., “Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging,” Radiology, vol. 253, no. 2, pp. 486–496, 2009. View at Publisher · View at Google Scholar · View at Scopus
  110. L. S. Hu, L. C. Baxter, K. A. Smith et al., “Relative cerebral blood volume values to differentiate high-grade glioma recurrence from posttreatment radiation effect: direct correlation between image-guided tissue histopathology and localized dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging measurements,” American Journal of Neuroradiology, vol. 30, no. 3, pp. 552–558, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. H. J. Baek, H. S. Kim, N. Kim, Y. J. Choi, and Y. J. Kim, “Percent change of perfusion skewness and kurtosis: a potential imaging biomarker for early treatment response in patients with newly diagnosed glioblastomas,” Radiology, vol. 264, no. 3, pp. 834–843, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. C. Choi, S. K. Ganji, R. J. DeBerardinis et al., “2-Hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas,” Nature Medicine, vol. 18, no. 4, pp. 624–629, 2012. View at Publisher · View at Google Scholar · View at Scopus
  113. M. Diehn, C. Nardini, D. S. Wang et al., “Identification of noninvasive imaging surrogates for brain tumor gene-expression modules,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 13, pp. 5213–5218, 2008. View at Publisher · View at Google Scholar · View at Scopus
  114. R. J. Young, A. Gupta, A. D. Shah et al., “Potential role of preoperative conventional MRI including diffusion measurements in assessing epidermal growth factor receptor gene amplification status in patients with glioblastoma,” American Journal of Neuroradiology, vol. 34, no. 12, pp. 2271–2277, 2013. View at Publisher · View at Google Scholar · View at Scopus
  115. M. C. Mabray, R. F. Barajas, and S. Cha, “Modern brain tumor imaging,” Brain Tumor Research and Treatment, vol. 3, no. 1, pp. 8–23, 2015. View at Publisher · View at Google Scholar
  116. W. Kaspera, K. Majchrzak, B. Bobek-Billewicz et al., “Reoperations of patients with low-grade gliomas in eloquent or near eloquent brain areas,” Neurologia i Neurochirurgia Polska, vol. 47, no. 2, pp. 116–125, 2013. View at Publisher · View at Google Scholar · View at Scopus
  117. K. Majchrzak, W. Kaspera, B. Bobek-Billewicz et al., “The assessment of prognostic factors in surgical treatment of low-grade gliomas: a prospective study,” Clinical Neurology and Neurosurgery, vol. 114, no. 8, pp. 1135–1144, 2012. View at Publisher · View at Google Scholar · View at Scopus
  118. A. Gupta, R. J. Young, A. D. Shah et al., “Pretreatment dynamic susceptibility contrast MRI perfusion in Glioblastoma: prediction of EGFR gene amplification,” Clinical Neuroradiology, vol. 25, no. 2, pp. 143–150, 2014. View at Publisher · View at Google Scholar · View at Scopus
  119. B. M. Ellingson, T. F. Cloughesy, W. B. Pope et al., “Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas,” NeuroImage, vol. 59, no. 2, pp. 908–916, 2012. View at Publisher · View at Google Scholar · View at Scopus
  120. P. Korfiatis, T. L. Kline, L. Coufalova et al., “MRI texture features as biomarkers to predict MGMT methylation status in glioblastomas,” Medical Physics, vol. 43, no. 6, pp. 2835–2844, 2016. View at Publisher · View at Google Scholar · View at Scopus
  121. V. A. Larsen, H. J. Simonsen, I. Law, H. B. W. Larsson, and A. E. Hansen, “Evaluation of dynamic contrast-enhanced T1-weighted perfusion MRI in the differentiation of tumor recurrence from radiation necrosis,” Neuroradiology, vol. 55, no. 3, pp. 361–369, 2013. View at Publisher · View at Google Scholar · View at Scopus
  122. W. B. Pope, X. J. Qiao, H. J. Kim et al., “Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study,” Journal of Neuro-Oncology, vol. 108, no. 3, pp. 491–498, 2012. View at Publisher · View at Google Scholar · View at Scopus
  123. B. M. Ellingson, T. F. Cloughesy, T. Zaw et al., “Functional diffusion maps (fDMs) evaluated before and after radiochemotherapy predict progression-free and overall survival in newly diagnosed glioblastoma,” Neuro-Oncology, vol. 14, no. 3, pp. 333–343, 2012. View at Publisher · View at Google Scholar · View at Scopus
  124. T. Singhal, T. K. Narayanan, M. P. Jacobs, C. Bal, and J. C. Mantil, “11C-methionine PET for grading and prognostication in gliomas: a comparison study with 18F-FDG PET and contrast enhancement on MRI,” Journal of Nuclear Medicine, vol. 53, no. 11, pp. 1709–1715, 2012. View at Publisher · View at Google Scholar · View at Scopus
  125. G. Pöpperl, F. W. Kreth, J. H. Mehrkens et al., “FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 34, no. 12, pp. 1933–1942, 2007. View at Publisher · View at Google Scholar · View at Scopus
  126. S. Kim, J. K. Chung, S. H. Im et al., “11C-methionine PET as a prognostic marker in patients with glioma: comparison with 18F-FDG PET,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 32, no. 1, pp. 52–59, 2005. View at Publisher · View at Google Scholar · View at Scopus
  127. D. Pauleit, F. Floeth, K. Hamacher et al., “O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas,” Brain, vol. 128, no. 3, pp. 678–687, 2005. View at Publisher · View at Google Scholar · View at Scopus
  128. B. J. Fueger, J. Czernin, T. Cloughesy et al., “Correlation of 6-18F-fluoro-L-dopa PET uptake with proliferation and tumor grade in newly diagnosed and recurrent gliomas,” Journal of Nuclear Medicine, vol. 51, no. 10, pp. 1532–1538, 2010. View at Publisher · View at Google Scholar · View at Scopus
  129. A. M. Spence, M. Muzi, K. R. Swanson et al., “Regional hypoxia in glioblastoma multiforme quantified with [18F] fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival,” Clinical Cancer Research, vol. 14, no. 9, pp. 2623–2630, 2008. View at Publisher · View at Google Scholar · View at Scopus
  130. L. W. Xu, K. K. Chow, M. Lim, and G. Li, “Current vaccine trials in glioblastoma: a review,” Journal of Immunology Research, vol. 2014, Article ID 796856, 10 pages, 2014. View at Publisher · View at Google Scholar
  131. T. Siegal, “Clinical impact of molecular biomarkers in gliomas,” Journal of Clinical Neuroscience, vol. 22, no. 3, pp. 437–444, 2015. View at Publisher · View at Google Scholar · View at Scopus
  132. A. A. Brandes, E. Franceschi, A. Tosoni et al., “MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients,” Journal of Clinical Oncology, vol. 26, no. 13, pp. 2192–2197, 2008. View at Publisher · View at Google Scholar · View at Scopus
  133. H. Shao, J. Chung, L. Balaj et al., “Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy,” Nature Medicine, vol. 18, no. 12, pp. 1835–1840, 2012. View at Publisher · View at Google Scholar · View at Scopus
  134. J. Skog, T. Würdinger, S. van Rijn et al., “Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers,” Nature Cell Biology, vol. 10, no. 12, pp. 1470–1476, 2008. View at Publisher · View at Google Scholar · View at Scopus
  135. Y. Chen, F. Hu, Y. Zhou, W. Chen, H. Shao, and Y. Zhang, “MGMT promoter methylation and glioblastoma prognosis: a systematic review and meta-analysis,” Archives of Medical Research, vol. 44, no. 4, pp. 281–290, 2013. View at Publisher · View at Google Scholar · View at Scopus
  136. A. L. Rivera, C. E. Pelloski, M. R. Gilbert et al., “MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma,” Neuro-Oncology, vol. 12, no. 2, pp. 116–121, 2010. View at Publisher · View at Google Scholar
  137. M. E. Hegi, L. Liu, J. G. Herman et al., “Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity,” Journal of Clinical Oncology, vol. 26, no. 25, pp. 4189–4199, 2008. View at Publisher · View at Google Scholar · View at Scopus
  138. M. A. Hammoud, R. Sawaya, W. Shi, P. F. Thall, and N. E. Leeds, “Prognostic significance of preoperative MRI scans in glioblastoma multiforme,” Journal of Neuro-Oncology, vol. 27, no. 1, pp. 65–73, 1996. View at Publisher · View at Google Scholar · View at Scopus
  139. C. X. Wu, G. S. Lin, Z. X. Lin et al., “Peritumoral edema on magnetic resonance imaging predicts a poor clinical outcome in malignant glioma,” Oncology Letters, vol. 10, no. 5, pp. 2769–2776, 2015. View at Publisher · View at Google Scholar · View at Scopus
  140. W. Wick, C. Meisner, B. Hentschel et al., “Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation,” Neurology, vol. 81, no. 17, pp. 1515–1522, 2013. View at Publisher · View at Google Scholar · View at Scopus
  141. M. Weller, R. Stupp, M. E. Hegi et al., “Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice,” Neuro-Oncology, vol. 14, supplement 4, pp. iv100–iv108, 2012. View at Publisher · View at Google Scholar · View at Scopus