Skip to main content
SpringerLink
Log in

Non-cytotoxic Therapies for Malignant Gliomas

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Malignant gliomas cause 2% of cancer deaths in western countries, and even the most intensive combinations of radiotherapy and chemotherapy cannot be curative. New chemotherapeutic drugs and alternative therapeutic modalities are strongly needed. Huge efforts are directed towards the development of innovative strategies for targeting and mending the specific molecular alterations in tumor cells (translational research). This review aims to summarize the most promising lines of investigational research in the field of neuro-oncology, such as non-cytotoxic drugs, immunotoxins, inhibitors of angiogenesis and gene therapy approaches, which will probably offer new therapy options for brain tumor patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brandes AA, Palmisano V, Pasetto LM, Basso U, Monfardini S: High-dose chemotherapy with bone marrow rescue for high-grade gliomas in adults. Cancer Invest 19: 41-48, 1996

    Google Scholar 

  2. Brandes AA, Rigon A, Zampieri P, Scelzi E, Amista P, Berti F, Rotilio A, Gardiman M, Fiorentino MV: Early chemotherapy and concurrent radio-chemotherapy in high grade glioma. J Neuro-Oncol 30: 247-255, 1996

    Google Scholar 

  3. Brandes AA, Pasetto LM, Monfardini S: Newdrugs in recurrent high grade gliomas. Anticancer Res 20: 1913-1920, 2000

    Google Scholar 

  4. Rasheed BKA, Wiltshire RN, Bigner SH, Bigner DD: Molecular pathogenesis of malignant gliomas. Curr Opin Oncol 11: 162-167, 1999

    Google Scholar 

  5. Coyle T, Levante S, Shetler M, Winfield J: In vitro and in vivo cytotoxicity of gossypol against central nervous system tumor cell lines. J Neuro-Oncol 19: 25-34, 2000

    Google Scholar 

  6. Bushunow P, Reidenberg MM, Wasenko J, Winfield J, Lorenzo B, Lemke S, Himpler B, Corona R, Coyle T: Gossypol treatment of recurrent adult malignant gliomas. J Neuro-Oncol 43: 79-86, 1999

    Google Scholar 

  7. Thibault A, Cooper MR, Figg WD, Venzon DJ, Sartor AO, Tompkins AC, Weinberger MS, Headlee DJ, McCall NA, Samid D: A phase I and pharmacokinetic study of intravenous phenylacetate in patients with cancer. Cancer Res 54: 1690-1694, 1994

    Google Scholar 

  8. Stockhammer G, Manley GT, Johnson R, Rosenblum MK, Samid D, Lieberman FS: Inhibition of proliferation and induction of differentiation in medulloblastomaand astrocytoma-derived cell lines with phenylacetate. J Neurosurg 83: 672-681, 1995

    Google Scholar 

  9. Ram Z, Samid D, Walbridge S, Oshiro EM, Viola JJ, Tao-Cheng JH, Shack S, Thibault A, Myers CE, Oldfield EH: Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate. Cancer Res 54: 2923-2927, 1994

    Google Scholar 

  10. Chang SM, Kuhn JG, Robins HI, Schold SC, Spence AM, Berger MS, Mehta MP, Bozik ME, Pollack I, Schiff D, Gilbert M, Rankin C, Prados MD: Phase II study of phenylacetate in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report. J Clin Oncol 13: 984-990, 1999

    Google Scholar 

  11. Carpentier AF, Leonard N, Lacombe J, Zassadowski F, Padua RA, Degos L, Daumas-Duport C, Chomienne C: Retinoic acid modulates RAR alpha and RAR beta receptors in human glioma cell lines. Anticancer Res 19: 3189-3192, 1999

    Google Scholar 

  12. Papagikos MA, Watson G: Retinoic acid receptor expression in human glioblastoma cell lines and modulation by exposure to all trans-retinoic acid of 9-cis-retinoic acid. Neuro-Oncology 2: 285, 2000

    Google Scholar 

  13. Yung WK, Kyritsis AP, Gleason MJ, LevinVA: Treatment of recurrent malignant gliomas with high-dose 13-cis-retinoic acid. Clin Cancer Res 2: 1931-1935, 1996

    Google Scholar 

  14. Jaeckle KA, Yung WKA, Prados MD, Hess KR: Phase II evaluation of temozolomide and 13-cis Retinoic acid for the treatment of recurrent and progressive malignant gliomas. Neuro-Oncology 2: 271, 2000

    Google Scholar 

  15. Kohn EC, Felder CC, Jacobs W, Holmes KA, Day A, Freer R, Liotta LA: Structure-function analysis of signal and growth inhibition by carboxyamido-triazole, CAI. Cancer Res 54: 935-942, 1994

    Google Scholar 

  16. Kohn EC, Figg WD, Sarosy GA, Bauer KS, Davis PA, Soltis MJ, Thompkins A, Liotta LA, Reed E: Phase I trial of micronized formulation carboxyamidotriazole in patients with refractory solid tumors: pharmacokinetics, clinical outcome, and comparison of formulations. J Clin Oncol 15: 1985-1993, 1997

    Google Scholar 

  17. Jacobs W, Mikkelsen T, Smith R, Nelson K, Rosenblum ML, Kohn EC: Inhibitory effects of CAI in glioblastoma growth and invasion. J Neuro-Oncol 32: 93-101, 1997

    Google Scholar 

  18. Joensuu J, Dimitrijevic S: Tyrosine kinase inhibitor imatinib (STI571) as an anticancer agent for solid tumours. Ann Med 33: 451-455, 2001

    Google Scholar 

  19. Kilic T. Alberta JA, Zdunek M, Acar M, Iannarelli P, O'Reilly T, Buchdunger E, Black PM, Stiles CD: Intracranial inhibition of Platelet derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res 60: 5143-5150, 2000

    Google Scholar 

  20. Barker FG, Simmons ML, Chang SM, Prados MD, Larson DA, Sneed PK, Wara WM, Berger MS, Chen P, Israel MA, Aldape KD: EGFR overexpression and radiation response in glioblastoma multiforme. Int J Radiat Oncol Biol Phys 51: 410-418, 2001

    Google Scholar 

  21. Arteaga CL, Johnson DH: Tyrosine kinase inhibitors-FD1839 (Iressa). Curr Opin Oncol 13: 491-498, 2001

    Google Scholar 

  22. Ciardiello F, Caputo R, Bianco R: Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin Cancer Res 7: 1459-1465, 2001

    Google Scholar 

  23. Heimberger AB, Archer GE, McLendon RE, Price D, Friedman AH, Friedman HS, Bigner DD, Sampson JH: Oral administration of the specific EGFR tyrosine kinase inhibitor, ZD1839 (IressaTM), is active against EGFR-overexpressing intracranial tumours. Clin Cancer Res 6S: 380, 2000

    Google Scholar 

  24. Fine HA, Figg WD, Jaeckle K, Wen PY, Kyritsis AP, Loeffler JS, Levin VA, Black PM, Kaplan R, Pluda JM, Yung WK: Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol 18: 708-715, 2000

    Google Scholar 

  25. Marx GM, Pavlakis N, McCowatt S, Boyle FM, Levi JA, Bell DR, Cook R, Biggs M, Little N, Wheeler HR: Phase II study of thalidomide in the treatment of recurrent glioblastoma multiforme (GBM). J Neuro-Oncol 54: 31-38, 2001

    Google Scholar 

  26. Bernsen HJA, van der Kogel AJ: Antiangiogenic therapy in brain tumor models. J Neuro-Oncol 45: 247-255, 1999

    Google Scholar 

  27. Groves MD, Jaeckle KA, Puduvalli VK, Hess KR, Yung WKA, Levian VA: A phase II study of temozolomide (Temodar) plus Marimastat for recurrent glioblastoma multiforme (GBM). Neuro-Oncology 2: 266, 2000

    Google Scholar 

  28. Parney IF, Farr-Jones MA, Chang LJ, Petruk KC: Human glioma immunobiology in vitro: implications for immunogene therapy. Neurosurgery 46: 1169-1177, 2000

    Google Scholar 

  29. Rajkumar SV, Buckner JC, Schomberg PJ, Cascino TL, Burch PA, Dinapoli RP: Phase I evaluation of radiation combined with recombinant interferon alpha-2a and BCNU for patients with high-grade glioma. Int J Radiat Oncol Biol Phys 40: 297-302, 1998

    Google Scholar 

  30. Buckner JC, Brown LD, Kuglet JW: Phase II evaluation of recombinant Interferon alpha and BCNU in recurrent glioma J Neurosurg 82: 430-435, 1995

    Google Scholar 

  31. Brandes AA, Scelzi E, Zampieri P, Rigon A, Rotilio A, Amista P, Berti F, Fiorentino MV: Phase II trial with BCNU plus alpha interferon in patients with recurrent high-grade gliomas. Am J Clin Oncol 20: 364-367, 1997

    Google Scholar 

  32. Buckner JC, Schomberg PJ, McGinnis WL, Cascino TL, Scheithauer BW, O'Fallon JR, Morton RF, Kuross SA, Mailliard JA, Hatfield AK, Cole JT, Steen PD, Bernath AM: A phase III study of radiation therapy plus carmustine with or without recombinant interferon-č in the treatment of patients with newly diagnosed high-grade glioma. Cancer 92: 420-433, 2001

    Google Scholar 

  33. Chang SM, Barker FG II, Huhn SL, Niocholas MK, Page M, Rabbit J, Prados MD: High dose oral tamoxifen and subcutaneous interferon alpha-2a for recurrent glioma. J Neuro-Oncol 37: 169-176, 1998

    Google Scholar 

  34. Hayes RL, Koslow M, Hiesiger EM, Hymes KB, Hochster HS, Moore EJ, Pierz DM, Chen DK, Budzilovich GN, Ransohoff J: Improved long term survival after intracavitary interleukin-2 lymphokine-activated killer cells for adults with recurrent malignant glioma. Cancer 76: 840-852, 1995

    Google Scholar 

  35. Plautz GE, Barnett GH, Miller DW, Cohen BH, Prayson RA, Krauss JC, Luciano M, Kangisser DB, Shu S: Systemic T cell adoptive immunotherapy of malignant gliomas. J Neurosurg 89: 42-51, 1998

    Google Scholar 

  36. Yu JS, Wheeler CJ, Zeltzer PM, Ying H, Finger DN, Lee PK, Yong WH, Incardona F, Thompson RC, Riedinger MS, Zhang W, Prins RM, Black KL: Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res 61: 842-847, 2001

    Google Scholar 

  37. Hall WA: Targeted toxin therapy for malignant astrocytoma. Neurosurgery 46: 544-551, 2000

    Google Scholar 

  38. Laske DW, Youle RJ, Oldfied EH: Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med 3: 1362-1368, 1997

    Google Scholar 

  39. Rand RW, Kreitman RJ, patronas N, Varrichhio F, Pastan I, Puri RK: Intratumoral administration of recombinant circularly permuted interleukin-4-Pseudomonas exotoxin in patients with high-grade glioma. Cancer Res 6: 2157-2165, 2000

    Google Scholar 

  40. Husain SR, Joshi BH, Puri RK: Interleukin-13 receptor as a unique target for anti-glioblastoma therapy. Int J Cancer 92: 168-175, 2001

    Google Scholar 

  41. Trepel M, Groscurth P, Malipiero U, Gulbins E, Dichgans J, Weller M: Chemosensitivity of human malignant glioma: modulation by p53 gene transfer. J Neuro-Oncol 39: 19-32, 1998

    Google Scholar 

  42. Feldman AL, Libutti SK: Progress in antiangiogenic gene therapy of cancer. Cancer 89: 1181-1184, 2000

    Google Scholar 

  43. Griscelli F, Li H, Bennaceur-Griscelli A, Soria J, Opolon P, Soria C, Perricaudet M, Yeh P, Lu H: Angiostatin gene transfer: inhibition of tumor growth in vivo by blockage of endothelial cell proliferation associated with a mitosis arrest. Proc Natl Acad Sci USA 95: 6367-6372, 1998

    Google Scholar 

  44. Ram Z, Culver KW, Oshiro EM, Viola JJ, DeVroom HL, Otto E, Long Z, ChiangY, McGarrity GJ, Muul LM, Katz D, Blaese RM, Oldfield EH: Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nat Med 3: 1354-1361, 1997

    Google Scholar 

  45. Izquierdo M, Martin V, de Felipe P, Izquierdo JM, Perez-Higueras A, Cortes ML, Paz JF, Isla A, Blazquez MG: Human malignant brain tumor response to herpes simplex thymidine kinase (HSVtk)/gancyclovir gene therapy. Gene Ther 3: 491-495, 1996

    Google Scholar 

  46. Sandmair AM, Limas S, Puranen P, Immonen A, Kossila M, Puranen M, Hurskainen H, Tyynela K, Turunen M, Vanninen R, Lehtolainen P, Paljarvi L, Johansson R, Vapalahti M, Yla-Herttuala S: Thymidine Kinase gene therapy for human malignant glioma, using replicationdeficient retroviruses or adenoviruses. Human Gene Ther 11: 2197-2205, 2000

    Google Scholar 

  47. Packer RJ, Raffel C, Villablanca JG, Tonn JC, Burdach SE, Burger K, Lafond D, McComb G, Cogen PH, Vezina G, Kapcala LP: Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration. J Neurosurg 92: 249-254, 2000

    Google Scholar 

  48. Palu G, Cavaggioni A, Calvi P, Franchin E, Pizzato M, Boschetto R, Parolin C, Chilosi M, Ferrini S, Zanusso A, Colombo F: Gene therapy of glioblastoma multiforme via combined expression of suicide and cytokine genes: a pilot study in humans. Gene Ther 6: 330-337, 1999

    Google Scholar 

  49. Okada H, Pollack IF, Lieberman F, Lunsford LD, Konziolka D, Schiff D, Attanucci J, Edington H, Chambers W, Kalinski P, Kinzler D, Whiteside T, Elder E, Potter D: Gene Therapy of malignant gliomas: a pilot study of vaccination with irradiated autologous glioma and dendritic cells admixed with IL-4 transduced fibroblasts to elicit an immune response. Human Gene Ther 12: 575-595, 2001

    Google Scholar 

  50. Engelhard HH: Antisense oligodeoxynucleotide technology: potential use for the treatment of malignant brain tumors. Cancer Control 5: 163-170, 1998

    Google Scholar 

  51. Heise CC, Williams AM, Xue S, Propst M, Kirn DH: Intravenous administration of ONYX-015, a selective replicating adenovirus, induces antitumoral efficay. Cancer Res 59: 2623-2628, 1999

    Google Scholar 

  52. Linke SP: Cancer. Has the smart bomb been defusedč Nature 395: 13, 1998

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Azienda Ospedale-Università of Padova, Padova, Italy

    Umberto Basso, Francesca Vastola & Alba A. Brandes

  2. Department of Neurological Sciences, Azienda Ospedale-Università of Padova, Padova, Italy

    Mario Ermani

Authors
  1. Umberto Basso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mario Ermani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesca Vastola
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alba A. Brandes
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Basso, U., Ermani, M., Vastola, F. et al. Non-cytotoxic Therapies for Malignant Gliomas. J Neurooncol 58, 57–69 (2002). https://doi.org/10.1023/A:1015839111005

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015839111005

Search

Navigation