Approaches to sensitizing glioblastoma to radiotherapy: Use of lentiviral vectors

  • Authors:
    • Teong Lip Chuah
    • David Gregory Walker
    • Ming Wei
    • Shaun Scott
    • Martin Francis Lavin
  • View Affiliations

  • Published online on: March 22, 2012     https://doi.org/10.3892/ijo.2012.1409
  • Pages: 1963-1969
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Abstract

Glioblastoma multiforme (GBM) is the most common primary brain tumour and extirpation followed by radio- and chemotherapy has had minimal impact on the median survival of patients which is still less than one year. Hence, a novel therapeutic modality is required if the survival of patients with this disease is to be improved. ATM, mutated in the human genetic disorder ataxia-telangiectasia (A-T), plays a central role in the response to DNA double strand breaks and patients with this disorder are characterised by extreme sensitivity to radiation, increased risk of cancer and neurodegeneration. Thus, ATM represents a potential target for radiosensitization of brain tumour cells. A safe, non-replicating lentivirus is used to abrogate ATM in GBM through the antisense and RNAi approaches for radiosensitization. With either techniques, ATM protein was reduced by >90% and there was a 3‑fold sensitization of GBM cells to radiation. ATM protein activation as well as ATM pS1981 foci formation were defective and downstream signalling determined by Ser15 phosphorylation on p53 was reduced. Success in the approaches provides a novel and exciting strategy for the treatment of GBM and thus improving the survival of patients with these tumours.

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June 2012
Volume 40 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Chuah TL, Walker DG, Wei M, Scott S and Lavin MF: Approaches to sensitizing glioblastoma to radiotherapy: Use of lentiviral vectors. Int J Oncol 40: 1963-1969, 2012
APA
Chuah, T.L., Walker, D.G., Wei, M., Scott, S., & Lavin, M.F. (2012). Approaches to sensitizing glioblastoma to radiotherapy: Use of lentiviral vectors. International Journal of Oncology, 40, 1963-1969. https://doi.org/10.3892/ijo.2012.1409
MLA
Chuah, T. L., Walker, D. G., Wei, M., Scott, S., Lavin, M. F."Approaches to sensitizing glioblastoma to radiotherapy: Use of lentiviral vectors". International Journal of Oncology 40.6 (2012): 1963-1969.
Chicago
Chuah, T. L., Walker, D. G., Wei, M., Scott, S., Lavin, M. F."Approaches to sensitizing glioblastoma to radiotherapy: Use of lentiviral vectors". International Journal of Oncology 40, no. 6 (2012): 1963-1969. https://doi.org/10.3892/ijo.2012.1409