Glioblastome multiforme (GBM) is the most common primary brain tumour in adults. Patients with GBM present with a variety of symptoms, including headaches, seizures, confusion, memory loss and personality changes. Most cases of GBM arise spontaneously without any preceding history of low-grade disease, and in the majority of patients there are no family genetic abnormalities that are known to cause GBM disease. Current treatment for GBM combines maximal surgical resection followed by radiotherapy and chemotherapy. Despite this aggressive therapy regime, patients diagnosed with GBM have median survival times of 14 months after diagnosis. Importantly, very recent studies show that mutations caused by the current therapy are directly responsible for the development of therapy resistant tumour cells, which then drive disease relapse and ultimately kill GBM patients. Increasing the effectiveness of current therapies will decrease therapy-induced mutations in tumours to extend patient lifespan and improve patient quality of life. We have identified a therapeutic strategy that increases the effectiveness of current therapy ten-fold in our experimental systems. The aim of our project is to confirm this important finding in tumour cells derived from a large number of patient tumours, and then generate the pre-clinical data necessary to establish a Phase I clinical trial. If the pre-clinical data supports our hypothesis we will apply for funding to establish a Phase I clinical trial at the Princess Alexandra Hospital in a follow-up grant in 2012. The funding provided by the Brain Foundation has the potential to significantly improve the clinical outcome in brain cancer patients. In addition, as the experimental work will be performed by a trainee neurosurgeon, the Brain Foundation is directly contributing to the training of the next generation of physician-researchers who will be spearheading translational medicine in the future.