Grant: Travel Awards - Institute Community Support

Glioblastoma multiforme (GBM) is a highly-invasive astrocytoma and accounts for >80% of all brain tumours. While rare, these tumours accounts for significant malignancy-related morbidity and mortality with a median survival time post-diagnosis of ~14.6 month and is often classified as a "high fatality cancer". Despite standardized GBM treatment, including surgery and chemo- (DNA alkylation) and radiotherapy, GBM prognoses are generally poor and rarely curable due to tumour recurrence (~6.9 months post-treatment) and resistance. As such, there is a critical requirement to dramatically improve upon current anti-GBM therapeutic strategies. We have developed a number of fluorescent GBM tumour cell lines with resistance to commonly used DNA damaging chemotherapeutic agents, including Temozolomide, Topotecan and Etoposide (TTE). These lines will be screened in a drug discovery platform with unique high-throughput DNA damage assay capability. By co-culturing fluorescently-labelled resistant and sensitive (parental) lines, the differential effects of drugs "hits" will be identified by the ratio difference of the fluorescence between the two strains. Our initial analysis will include interrogation of the FDA-approved library of chemical/drug compounds. Potential drug "hits" that show efficacy against TTE-resistant GBM will undergo secondary analysis including validation of resistance-specific drug killing, comparison of parental/resistance DNA damage responses and additional biochemical/mechanistic studies. The identification of FDA-approved drugs for the treatment of resistant GBM is a clinically expedient approach of drug repurposing. In addition to immediate clinical use, this strategy may yield additional treatments against other tumours that develop resistance to any one of the commonly used TTE agents.