The most severe form of brain cancer, Glioblastoma is extremely lethal; with the average survival time of less than 15 months after diagnosis. Treating glioblastoma patients involve initial Surgery to remove the majority of tumour. However, in almost all cases the residual tumour cells continue to divide uncontrollably, leading to tumour re-establishment called tumour recurrence ultimately causing patient mortality. Current treatment after surgery commonly includes the use of radiotherapy and temozolomide. However, these therapies and other additional anti-cancer agents have proven to be generally unsuccessful in enhancing patient survival. Therefore, it is critical to identify the key genetic and molecular alterations promoting Glioblastoma progression and resistance and a critical need to find therapeutic agents that will prolong the survival times of patients with glioblastoma.
In this study, we have analysed the expression levels of over 800 micro RNA (miRNA) species with the aim to determine differential miRNAs expression profiles in 6 glioblastoma cell lines prior or after treatment with radiotherapy and temozolomide. In addition, we have tested the inhibitory effects of 1172 FDA-approved agents on glioblastoma cell lines. We have identified several “lead” candidate agents based on their ability to inhibit resistant glioblastoma cell lines. Further testing in several in vitro and in vivo based models are currently underway. Our experiments outlined here are expected to add significantly to the current knowledge of the molecular mechanism of glioblastoma progression and resistance to therapy. We also expect that our data will provide proof-of-principle evidence for the use of novel agents in the treatment of glioblastoma patients. Importantly, these agents have been clinically approved for human disease, and thus will be fast-tracked for the treatment of patients with glioblastoma.