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AssigneeCouncil of Scientific and Industrial Research
InventorsSomasundaram Kumaravel, Arivazhagan Arimappamagan, Kandavel Thennarasu, Alangar Sathyaranjandas Hegde, Ashwathnarayana Chandramouli, Santosh Vani, Paturu Kondaiah, Satyanarayana Rao Manchanahalli Rangaswamy
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The present invention provides a TOP2A inhibition by temozolomide useful for predicting glioblastoma patient's survival. Glioblastoma (GBM) is the most common, malignant primary adult brain tumor. The conventional treatments for GBM, include surgery, radiation, and chemotherapy which have only modestly improved patient survival. The patients with GBM expressing higher TOP2A transcript levels had better prognosis. More interestingly, the present invention reports that temozolomide is an inhibitor of TOP2A activity in vitro. The present invention further shows that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. Thus it is demonstrated for the first time that temozolomide is a TOP2A inhibitor and establishes that TOP2A transcript levels determines the chemosensitivity of glioblastoma to temozolomide therapy thus explaining the very high levels of TOP2A transcript being a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.
1) An in vitro method of determining prognosis of glioblastoma, wherein the said method comprises determining the level of expression of the gene TOP2A in a test sample and in a control sample, wherein a higher level of expression of TOP2A in the test sample, as compared to the control sample, indicates good prognosis of glioblastoma.
4) A method of detecting cytotoxicity of temozolomide in glioblastoma patients wherein cells with low concentration of TOP2A protein is less sensitive to temozolomide than cells containing high concentration of TOP2A.
6) A kit for determining the prognosis of glioblastoma in a human subject undergoing temozolomide therapy, wherein the said kit comprises:
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