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

胶质母细胞瘤是最常见的脑肿瘤类型之一。它是一种非常具有侵袭性的癌症，目前无法治愈，尽管有手术，化疗和放疗治疗。它如此难以治疗的一个重要原因是因为肿瘤细胞具有高度侵袭性。它们扩散到周围健康的脑组织中，以至于肿瘤无法通过手术完全切除。正常大脑的入侵也会导致破坏性的神经和认知症状。放射治疗是胶质母细胞瘤患者治疗的重要组成部分，尽管它不能治愈，但它可以延长大多数患有这种疾病的患者的预期寿命。然而，最近，包括我们在内的一些研究人员发现，放射治疗可以增加治疗后存活的肿瘤细胞侵入大脑的能力。这种以前未知的效应可能是我们无法治愈胶质母细胞瘤的部分原因，也是它不断扩散到健康大脑的部分原因。我们的研究小组最近发现了一种关键分子MRCK，它参与促进肿瘤细胞侵入大脑，并表明用一种特殊设计的药物阻断MRCK的活性可以防止放射治疗刺激这种侵入。我们现在建议进行更详细的研究，以揭示将放射治疗与MRCK功能和胶质母细胞瘤细胞的侵袭行为联系起来的复杂机制。我们的研究结果将确定新的治疗方法，可以与放射治疗相结合，以改善胶质母细胞瘤患者的预后。与此同时，我们希望确定分子“签名”，这将告诉我们哪些患者最有可能从这些新治疗中受益。

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.