Novel therapies for high-grade gliomas: A vision for future

Abstract

The treatment for high-grade glioma remains an enigma. The standard treatment using surgery, radiation therapy and chemotherapy for such highly malignant lesions has only yielded modest results, in terms of survival and improving the quality of life of patients. Less than 10% of such patients survive beyond two years. All conventional therapies have failed to increase the survival beyond this extent. There has been a growing interest in the molecular approaches for the treatment of high-grade gliomas which include gene therapy, oncolytic virotherapy, and immunotherapy. These new therapies are in preclinical and investigational stages. They may not substitute the conventional therapies; they may not be the ultimate elixir for this deadly disease. However, in the coming years, they are likely to have synergistic and complimentary roles alongside conventional therapies. Through this paper, we have attempted to highlight the rationale behind gene therapy which can be used for cytotoxic approaches, immunomodulation strategy, and targeted toxin delivery in the tumor cell. We have reviewed current available literature and through this paper focus on reporting such therapeutic options, their potential usage, benefits and limitations.

Key words

Current studies - gene therapy - malignant glioma - novel therapy

• References

• 1 Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M. et al Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res 2010; 16: 2443-2449
• 2 Kroeger KM, Muhammad AK, Baker GJ, Assi H, Wibowo MK, Xiong W. et al Gene therapy and virotherapy: Novel therapeutic approaches for brain tumors. Discov Med 2010; 10: 293-304
• 3 Wen PY, Kesari S. Malignant gliomas in adults. N EnglJ Med 2008; 359: 492-507
• 4 Clarke J, Butowski N, Chang S. Recent advances in therapy for glioblastoma. Arch Neurol 2010; 67: 279-283
• 5 Quinn JA, Jiang SX, Reardon DA, Desjardins A, Vredenburgh JJ, Rich JN. et al Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma. J Clin Oncol 2009; 27: 1262-1267
• 6 Clarke JL, Iwamoto FM, Sul J, Panageas K, Lassman AB, DeAngelis LM. et al Randomized phasell trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glioblastoma. J Clin Oncol 2009; 27: 3861-3867
• 7 Mattei TA, Ramina R, Miura FK, Aguiar PH, Valiengo Lda C. Genetic therapy in gliomas: Historical analysis and future perspectives. Neurol India 2005; 53: 17-26
• 8 Chi AS, Wen PY. Inhibiting kinases in malignant gliomas. Expert Opin Ther Targets 2007; 11: 473-496
• 9 Kim SK, Wang KC, Cho BK, Chung HT, Kim YY, Lim SY. et al Interaction between p53 and p16 expressed by adenoviral vectors in human malignant glioma cell lines. J Neurosurg 2002; 97: 143-150
• 10 Fueyo J, Gomez-Manzano C, Yung WK, Liu TJ, Alemany R, Bruner JM. et al Suppression of human glioma growth by adenovirusmediated Rb gene transfer. Neurology 1998; 50: 1307-1315
• 11 Curtin JF, King GD, Candolfi M, Greeno RB, Kroeger KM, Lowenstein PR. et al Combining cytotoxic and immune-mediated gene therapy to treat brain tumors. Curr Top Med Chem 2005; 5: 1151-1170
• 12 Roth W, Weller M. Chemotherapy and immunotherapy of malignant glioma: Molecular mechanisms and clinical perspectives. Cell Mol Life Sci 1999; 56: 481-506
• 13 Xia S, Rosen EM, Laterra J. Sensitization of glioma cells to Fas-dependent apoptosis by chemotherapy-induced oxidative stress. Cancer Res 2005; 65: 5248-5255
• 14 Shah K, Tung CH, Breakefield XO, Weissleder R. In vivo imaging of S-TRAIL-mediated tumor regression and apoptosis. Mol Ther 2005; 11: 926-931
• 15 Jendrossek V, Belka C, Bamberg M. Novel chemotherapeutic agents for the treatment of glioblastoma multiforme. Expert Opin Investig Drugs 2003; 12: 1899-1924
• 16 Kuan CT, Wikstrand CJ, Bigner DD. EGF mutant receptor vIII as a molecular target in cancer therapy. Endocr Relat Cancer 2001; 8: 83-96
• 17 Kesari S, Ramakrishna N, Sauvageot C, Stiles CD, Wen PY. Targeted molecular therapy of malignant gliomas. Curr Neurol Neurosci Rep 2005; 5: 186-197
• 18 Rich JN, Reardon DA, Peery T, Dowell JM, Quinn JA, Penne KL. etal Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol 2004; 22: 133-142
• 19 Haas-Kogan DA, Prados MD, Tihan T, Eberhard DA, Jelluma N, Arvold ND. et al Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib. J Natl Cancer Inst 2005; 97: 880-887
• 20 Omay SB, Vogelbaum MA. Current concepts and newer developments in the treatment of malignant gliomas. Indian J Cancer 2009; 46: 88-95
• 21 Traxler P, Allegrini PR, Brandt R, Brueggen J, Cozens R, Fabbro D. et al AEE788: A dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res 2004; 64: 4931-4941
• 22 Spector NL, Xia W, Burris 3rd H, Hurwitz H, Dees EC, Dowlati A. et al Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. J Clin Oncol 2005; 23: 2502-2512
• 23 Fukumura D, Xu L, Chen Y, Gohongi T, Seed B, Jain RK. Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo . Cancer Res 2001; 61: 6020-6024
• 24 Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I. et al PhaseII trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2009; 27: 740-745
• 25 Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE. et al Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009; 27: 4733-4740
• 26 Reardon DA, Dresemann G, Taillibert S, Campone M, van den Bent M, Clement P. et al Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. BrJ Cancer 2009; 101: 1995-2004
• 27 Razis E, Selviaridis P, Labropoulos S, Norris JL, Zhu MJ, Song DD. et al Phase II study of neoadjuvant imatinib in glioblastoma: Evaluation of clinical and molecular effects of the treatment. Clin Cancer Res 2009; 15: 6258-6266
• 28 Holdhoff M, Kreuzer KA, Appelt C, Scholz R, Na IK, Hildebrandt B. et al Imatinib mesylate radiosensitizes human glioblastoma cells through inhibition of platelet-derived growth factor receptor. Blood Cells Mol Dis 2005; 34: 181-185
• 29 Cloughesy TF, Wen PY, Robins HI, Chang SM, Groves MD, Fink KL. et al Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: A North American Brain Tumor Consortium Study. J Clin Oncol 2006; 24: 3651-3656
• 30 Galanis E, Buckner JC, Maurer MJ, Kreisberg JI, Ballman K, Boni J. et al PhaseII trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: A North Central Cancer Treatment Group Study. J Clin Oncol 2005; 23: 5294-5304
• 31 Galanis E, Jaeckle KA, Maurer MJ, Reid JM, Ames MM, Hardwick JS. et al Phase II trial of vorinostat in recurrent glioblastoma multiforme: A north central cancer treatment group study. J Clin Oncol 2009; 27: 2052-2058
• 32 Dey M, Ulasov IV, Lesniak MS. Virotherapy against malignant glioma stem cells. Cancer Lett 2010; 289: 1-10
• 33 Sandmair AM, Loimas S, Puranen P, Immonen A, Kossila M, Puranen M. et al Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. Hum Gene Ther 2000; 11: 2197-2205
• 34 Hardcastle J, Kurozumi K, Dmitrieva N, Sayers MP, Ahmad S, Waterman P. et al Enhanced antitumor efficacy of vasculostatin (Vstat120) expressing oncolytic HSV-1. Mol Ther 2010; 18: 285-294
• 35 Yoo JY, Kim JH, Kwon YG, Kim EC, Kim NK, Choi HJ. et al VEGF-specific short hairpin RNA-expressing oncolytic adenovirus elicits potent inhibition of angiogenesis and tumor growth. MolTher 2007; 15: 295-302
• 36 Liu TC, Zhang T, Fukuhara H, Kuroda T, Todo T, Martuza RL. et al Oncolytic HSV armed with platelet factor 4 an antiangiogenic agent shows enhanced efficacy. Mol Ther 2006; 14: 789-797
• 37 Terada K, Wakimoto H, Tyminski E, Chiocca EA, Saeki Y. Development of a rapid method to generate multiple oncolytic HSV vectors and their In vivo evaluation using syngeneic mouse tumor models. GeneTher 2006; 13: 705-714
• 38 Han ZQ, Assenberg M, Liu BL, Wang YB, Simpson G, Thomas S. et al Development of a second-generation oncolytic Herpes simplex virus expressing TNFalpha for cancer therapy. J Gene Med 2007; 9: 99-106
• 39 Forsyth P, Roldan G, George D, Wallace C, Palmer CA, Morris D. et al A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas. Mol Ther 2008; 16: 627-632
• 40 Msaouel P, Dispenzieri A, Galanis E. Clinical testing of engineered oncolytic measles virus strains in the treatment of cancer: An overview. Curr Opin Mol Ther 2009; 11: 43-53
• 41 Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: From immunosurveillance to tumor escape. Nat Immunol 2002; 3: 991-998
• 42 Young HF, Sakalas R, Kaplan AM. Inhibition of cell-mediated immunity in patients with brain tumors. Surg Neurol 1976; 5: 19-23
• 43 Ehtesham M, Black KL, Yu JS. Recent progress in immunotherapy for malignant glioma: treatment strategies and results from clinical trials. Cancer Control 2004; 11: 192-207
• 44 Gomez GG, Kruse CA. Mechanisms of malignant glioma immune resistance and sources of immunosuppression. GeneTherMolBiol 2006; 10: 133-146
• 45 Yang I, Han SJ, Kaur G, Crane C, Parsa AT. The role of microglia in central nervous system immunity and glioma immunology. J Clin Neurosci 2010; 17: 6-10
• 46 Puri S, Mahapatra AK, Hussain E, Sarkar C, Sinha S, Joshi BH. A review of studies on targeting interleukin 4 receptor for central nervous system malignancy. Curr Mol Med 2009; 9: 732-739
• 47 Rodrigues JC, Gonzalez GC, Zhang L, Ibrahim G, Kelly JJ, Gustafson MP. et al Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties. Neuro Oncol 2010; 12: 351-365
• 48 Wikstrand CJ, Cokgor I, Sampson JH, Bigner DD. Monoclonal antibody therapy of human gliomas: Current status and future approaches. Cancer Metastasis Rev 1999; 18: 451-464
• 49 Brady LW, Miyamoto C, Woo DV, Rackover M, Emrich J, Bender H. et al Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial. Int J Radiat Oncol Biol Phys 1992; 22: 225-230
• 50 Kalofonos HP, Pawlikowska TR, Hemingway A, Courtenay-Luck N, Dhokia B, Snook D. et al Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase. J Nucl Med 1989; 30: 1636-1645
• 51 Bigner DD, Brown M, Coleman RE, Friedman AH, Friedman HS, McLendon RE. et al Phase I studies of treatment of malignant gliomas and neoplastic meningitis with 131I-radiolabeled monoclonal antibodies anti-tenascin 81C6 and anti-chondroitin proteoglycan sulfate Me1-14 F (ab’)2-a preliminary report. J Neurooncol 1995; 24: 109-122
• 52 Riva P, Arista A, Franceschi G, Frattarelli M, Sturiale C, Riva N. et al Local treatment of malignant gliomas by direct infusion of specific monoclonal antibodies labeled with 131I: Comparison of the results obtained in recurrent and newly diagnosed tumors. Cancer Res 1995; 55 (23) Suppl 5952s-5956s
• 53 Hopkins K, Papanastassiou V, Kemshead JT. The treatment of patients with recurrent malignant gliomas with intratumoral radioimmunoconjugates. Recent Results Cancer Res 1996; 141: 159-175
• 54 Day ED, Lassiter S, Woodhall B, Mahaley JL, MahaleyMS Jr. The localization of radioantibodies in human brain tumors. I. Preliminary exploration. Cancer Res 1965; 25: 773-778
• 55 Mahaley Jr MS, Mahaley JL, Day ED. The localization of radioantibodies in human brain tumors. II. Radioautography. Cancer Res 1965; 25: 779-793
• 56 Hiserodt JC, Vujanovic NL, Reynolds CW, Herberman RB, Cramer DV. Studies on lymphokine activated killer cells in the rat: Analysis of precursor and effector cell phenotype and relationship to natural killer cells. Prog Clin Biol Res 1987; 244: 137-146
• 57 Hayes RL, Koslow M, Hiesiger EM, Hymes KB, Hochster HS, Moore EJ. et al Improved long term survival after intracavitary interleukin-2 and lymphokine-activated killer cells for adults with recurrent malignant glioma. Cancer 1995; 76: 840-852
• 58 Barba D, Saris SC, Holder C, Rosenberg SA, Oldfield EH. Intratumoral LAK cell and interleukin-2 therapy of human gliomas. J Neurosurg 1989; 70: 175-182
• 59 Merchant RE, Grant AJ, Merchant LH, Young HF. Adoptive immunotherapy for recurrent glioblastoma multiforme using lymphokine activated killer cells and recombinant interleukin-2. Cancer 1988; 62: 665-671
• 60 Okada H, Low KL, Kohanbash G, McDonald HA, Hamilton RL, Pollack IF. Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas. J Neurooncol 2008; 88: 245-250
• 61 Wykosky J, Gibo DM, Stanton C, Debinski W. Interleukin-13 receptor alpha 2, EphA2, and Fos-related antigen 1 as molecular denominators of high-grade astrocytomas and specific targets for combinatorial therapy. Clin Cancer Res 2008; 14: 199-208
• 62 Vogelbaum MA, Sampson JH, Kunwar S, Chang SM, Shaffrey M, Asher AL. et al Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: Phase 1 study of final safety results. Neurosurgery 2007; 61: 1031-1037 discussion 1037-8
• 63 Kunwar S, Prados MD, Chang SM, Berger MS, Lang FF, Piepmeier JM. et al Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: A report by the Cintredekin Besudotox Intraparenchymal Study Group. J Clin Oncol 2007; 25: 837-844
• 64 Kawakami K, Kawakami M, Kioi M, Husain SR, Puri RK. Distribution kinetics of targeted cytotoxin in glioma by bolus or convection-enhanced delivery in a murine model. J Neurosurg 2004; 101: 1004-1011