Investigating the role of the actin-myosin regulatory protein MRCK in promoting radiation induced infiltration by glioblastoma cells.

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Glioblastoma is one of the most common types of brain tumour. It is a very aggressive form of cancer and is currently incurable despite treatment with surgery, chemotherapy and radiotherapy. One important reason why it is so difficult to treat is because the tumour cells are highly invasive. They spread into the surrounding healthy brain tissue to such an extent that the tumours cannot be completely removed by surgery. Invasion of the normal brain also leads to devastating neurological and cognitive symptoms. Radiotherapy is a crucial part of treatment for patients with glioblastoma, and although it isn't curative, it increases life expectancy for most patients with this disease. Recently, however, several researchers including ourselves have found that radiotherapy can increase the ability of tumour cells that survive treatment to invade into the brain. This previously unknown effect might be partly responsible for our inability to cure glioblastoma, and for its relentless spread into the healthy brain.Our research group has recently identified a key molecule, MRCK, that is involved in promoting tumour cell invasion into the brain, and have shown that blocking the activity of MRCK with a specially designed drug can prevent radiotherapy from stimulating this invasion. We now propose to undertake more detailed research that will uncover the complex mechanisms that link radiotherapy with MRCK function and with the invasive behaviour of glioblastoma cells. The results of our research will identify new treatments that could be combined with radiotherapy to improve outcomes for patients with glioblastoma. At the same time we hope to identify molecular 'signatures' that will tell us which patients are most likely to benefit from these new treatments.