Dr Christine Hawkins, A/Professor David Ashley, Professor Henry Friedman
Murdoch Children's Research Institute
Research into the treatment of malignant glioma (brain) in adults. High-grade malignant glioma is a type of brain tumour that is currently incurable, with most patients dying within a year of diagnosis. Novel, more effective treatments are therefore urgently required.
TRAIL is an exciting novel candidate for treating cancers such as malignant glioma, as it kills cells through distinct pathways from those triggered by conventional anti-cancer treatments. Clinical trials of TRAIL and related agents are currently being conducted, and it seems likely that these agents will become clinically available.
To date, analyses of factors influencing glioma sensitivity to TRAIL have relied almost exclusively on long-established cell lines. It is presently unknown whether or not these indefinitely in vitro cultured lines accurately emulate the responses of gliomas within patients, and there are reasons to think that they may not. It is vital that we now investigate TRAIL sensitivity and signalling in glioma cells that have not adapted to tissue culture conditions.
In this study we aim to explore TRAIL and anti-TRAIL receptor signalling in freshly resected gliomas and early passage glioma cell lines, as these are likely to mimic characteristics of glioma cells in vivo. We will use in vitro analyses and mouse models to evaluate the factors influencing the sensitivity of glioma cells to TRAIL and agonistic antibodies.
This will help predict which patients are likely to benefit from treatment with TRAIL or related agents. Definition of these factors, and any potential mechanisms of resistance in ex vivo glioma cells, will therefore contribute to the development of diagnostic reagents. Our data may also assist in the development of potential therapeutic strategies to sensitise unresponsive tumours to TRAIL.
$70,000 per annum