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

MICA：GSK-3 作为胶质母细胞瘤治疗的多功能靶点；

• 批准号: MR/K015214/1
• 负责人: Susan Short
• 金额: $ 51.83万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK015214%2F1
• 关键词: MICA; GSK; multifunctional; target; glioblastoma

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.

高级别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脑。这些迁移的细胞使得手术完全切除肿瘤变得不可能，因此这种肿瘤的受害者的生存率特别差，绝大多数患者在诊断后存活不到两年。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用处。劳勒博士已经确定了一种通过作用于一种叫做GSK-3的特定细胞蛋白质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药物来阻止其作用。劳勒博士已经证明，这些药物也有效地阻止成人脑肿瘤细胞的迁移。阿斯利康已经开发出针对GSK-3的药物，用于治疗阿尔茨海默病。其中一种药物AZD 1080已经在人体中进行了测试，在这里，我们将进行研究，以确定它是否适用于胶质母细胞瘤的治疗-这种药物的新应用，这可能是将这种方法应用于临床的最快方法。这些模型中的活性证据将用于支持未来的临床试验，希望这项研究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。

项目成果

GSK-3 Inhibition Is Cytotoxic in Glioma Stem Cells through Centrosome Destabilization and Enhances the Effect of Radiotherapy in Orthotopic Models.

• DOI: 10.3390/cancers13235939
• 发表时间: 2021-11-25
• 期刊: Cancers
• 影响因子: 5.2
• 作者: Brüning-Richardson A;Shaw GC;Tams D;Brend T;Sanganee H;Barry ST;Hamm G;Goodwin RJA;Swales JG;King H;Steele L;Morton R;Widyadari A;Ward TA;Esteves F;Boissinot M;Mavria G;Droop A;Lawler SE;Short SC
• 通讯作者: Short SC

PO17A NOVEL IMMUNOHISTOCHEMICAL METHODOLOGY FOR THE INVESTIGATION OF STEM CELL-LIKE SUBPOPULATIONS IN GLIOMA SPHEROIDS AND MIGRATORY CELLS

PO17A 用于研究胶质瘤球体和迁移细胞中干细胞样亚群的新型免疫组织化学方法

• DOI: 10.1093/neuonc/nov284.14
• 发表时间: 2015
• 期刊: Neuro-Oncology
• 影响因子: 15.9
• 作者: Cheng V

ANGI-03. THE MIGRATORY SWITCH - INVESTIGATING MESENCHYMAL-AMOEBOID TRANSITION (MAT) IN HIGH GRADE GLIOMAS

安吉-03。

• DOI: 10.1093/neuonc/nox168.082
• 发表时间: 2017
• 期刊: Neuro-Oncology
• 影响因子: 15.9
• 作者: Taylor S

ANGI-14. A GSK-3/b-CATENIN/ARHGAP AXIS REGULATES GLIOBLASTOMA INVASION

ANGI-14。

• DOI: 10.1093/neuonc/nox168.092
• 发表时间: 2017
• 期刊: Neuro-Oncology
• 影响因子: 15.9
• 作者: Brüning-Richardson A

High-content analysis of tumour cell invasion in three-dimensional spheroid assays.

• DOI: 10.18632/oncoscience.171
• 发表时间: 2015
• 期刊: Oncoscience
• 作者: Cheng V;Esteves F;Chakrabarty A;Cockle J;Short S;Brüning-Richardson A
• 通讯作者: Brüning-Richardson A