Approaches to sensitizing glioblastoma to radiotherapy: Use of lentiviral vectors

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Author(s)
Chuah, Teong Lip
Walker, David Gregory
Wei, Ming
Scott, Shaun
Lavin, Martin Francis
Griffith University Author(s)
Year published
2012
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Show full item recordAbstract
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 ...
View more >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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View more >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.
View less >
Journal Title
International Journal of Oncology
Volume
40
Issue
6
Copyright Statement
© 2011 Spandidos Publications. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the conference's website for access to the definitive, published version.
Subject
Oncology and carcinogenesis
Cancer therapy (excl. chemotherapy and radiation therapy)