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

高级别胶质瘤是一种侵袭性的脑肿瘤，对成人和儿童都有影响。这些肿瘤的特点是肿瘤细胞对正常大脑的广泛渗透。这些迁移细胞使得手术不可能完全切除肿瘤，因此这种肿瘤的受害者的存活率特别低，绝大多数患者在确诊后无法存活超过两年。人们认为，一种针对侵袭大脑的肿瘤细胞的有效疗法将对治疗这种疾病大有裨益。劳勒博士已经确定了一种通过作用于一种名为GSK-3的特定细胞蛋白来阻止胶质母细胞瘤细胞迁移的策略。由于GSK-3与糖尿病和阿尔茨海默病等常见疾病有关，因此已开发出大量药物来阻止其作用。劳勒博士已经证明，这些药物也能有效地阻止成人脑瘤细胞的迁移。阿斯特拉-捷利康已经开发出针对GSK-3的药物，可能用于治疗阿尔茨海默病。其中一种药物AZD1080已经在人体上进行了测试，在这里我们将进行研究，以确定它是否适合治疗胶质母细胞瘤--这是这种药物的一种新应用，可能代表着这种方法进入临床的最快方式。AZD1080将在各种胶质母细胞瘤的实验室模型中进行测试，以及现有的治疗方法。这些模型的活性证据将被用来支持未来的临床试验。希望这项研究最终将有助于开发一种有效的临床方法来治疗胶质母细胞瘤。

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.