MICA: GSK-3 as a multifunctional target for glioblastoma treatment; Hitting multiple tumour hallmarks with a single drug.

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High grade gliomas are an aggressive type of brain tumour affecting both adults and children. These tumours arecharacterised by extensive infiltration of normal brain by tumour cells. These migrating cells render it impossible tocompletely remove the tumour surgically and as a consequence the survival for victims of this kind of tumour is particularlypoor, with the vast majority of patients not surviving beyond two years after diagnosis. It is thought that an effective therapythat targets the tumour cells that invade the brain would be of great use in treating this disease. Dr Lawler has identified astrategy that blocks glioblastoma cell migration by acting on a specific cellular protein called GSK-3. Because GSK-3 is implicated in common illnesses including diabetes and Alzheimer's disease, a large number of drugs have been developed that will block its action. Dr Lawler has shown that these drugs also potently block adult brain tumour cell migration. Astra-Zeneca have developeddrugs that target GSK-3 for potential use in the treatment of Alzheimer's disease. One of these drugs, AZD1080has been tested in humans, and here we will carry out studies that will determine whether it is suitable for the treatment of glioblastoma - a new application for this drug, which may represent the fastest way of getting this approach to the clinic.AZD1080 will be tested in a variety of laboratory models of glioblastoma alongside existing treatments. Evidence of activity in these models will be used to support future clinical trials.It is hoped that this study will ultimately contribute to the development of an effective clinical approach for the treatment of glioblastoma.