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

高度胶质瘤是一种侵袭性脑肿瘤，影响成人和儿童。这些肿瘤的特征是肿瘤细胞广泛浸润正常大脑。这些迁移的细胞使得手术无法完全切除肿瘤，因此这类肿瘤患者的生存率特别低，绝大多数患者在诊断后都活不过两年。人们认为，一种针对侵入大脑的肿瘤细胞的有效疗法将对治疗这种疾病大有帮助。劳勒博士已经确定了一种通过作用于一种叫做GSK-3的特殊细胞蛋白来阻止胶质母细胞瘤细胞迁移的策略。由于GSK-3与包括糖尿病和阿尔茨海默病在内的常见疾病有关，因此已经开发了大量可以阻断其作用的药物。劳勒博士已经证明，这些药物也能有效地阻止成人脑肿瘤细胞的迁移。Astra-Zeneca已经开发出针对GSK-3的药物，用于治疗阿尔茨海默病。其中一种药物azd1080已经在人体中进行了测试，我们将在这里进行研究，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，可能是将这种方法推向临床的最快途径。AZD1080将在各种胶质母细胞瘤的实验室模型中与现有的治疗方法一起进行测试。这些模型的活性证据将用于支持未来的临床试验。希望这项研究将最终有助于开发一种有效的治疗胶质母细胞瘤的临床方法。

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.