Approaches to sensitizing glioblastoma to radiotherapy: Use of lentiviral vectors

Chuah, Teong Lip, Walker, David Gregory, Wei, Ming, Scott, Shaun and Lavin, Martin Francis (2012) Approaches to sensitizing glioblastoma to radiotherapy: Use of lentiviral vectors. International Journal of Oncology, 40 6: 1963-1969. doi:10.3892/ijo.2012.1409

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Author Chuah, Teong Lip
Walker, David Gregory
Wei, Ming
Scott, Shaun
Lavin, Martin Francis
Title Approaches to sensitizing glioblastoma to radiotherapy: Use of lentiviral vectors
Journal name International Journal of Oncology   Check publisher's open access policy
ISSN 1019-6439
Publication date 2012-06
Sub-type Article (original research)
DOI 10.3892/ijo.2012.1409
Volume 40
Issue 6
Start page 1963
End page 1969
Total pages 7
Place of publication Athens, Greece
Publisher Spandidos Publications
Collection year 2013
Language eng
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.
Keyword Radiosensitization
Glioblastoma multiforme
Ataxia-telangiectasia mutated
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
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