Sami Arshawn, Karsy Michael
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA.
Tumour Biol. 2013 Aug;34(4):1991-2002. doi: 10.1007/s13277-013-0800-5. Epub 2013 Apr 30.
Glioblastoma multiforme (GBM) is a grade IV astrocytoma with a median survival of 12 months despite current multi-modal treatment options. GBM is distinguished clinicopathologically into primary and secondary subtypes. Mutations of phosphatase and tensin homolog, and subsequent upregulation of the downstream protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway, are commonly seen in primary GBM and less predominantly in secondary GBM. While investigations into targeted treatments of mTOR have been attempted, feedback regulation within the mTOR signaling pathway may account for therapeutic resistance. Currently, rapamycin analogs, dual-targeted mTOR complex 1 and 2 agents as well as dual mTOR and phosphatidylinositol-3 kinase-targeted agents are being investigated experimentally and in clinical trials. This review will discuss the experimental potential of these agents in the treatment of GBM and their current stage in the GBM drug pipeline. Knowledge obtained from the application of these agents can help in understanding the pathogenesis of GBM as well as delineating subsequent treatment strategies.
多形性胶质母细胞瘤（GBM）是一种IV级星形细胞瘤，尽管目前有多种联合治疗方案，但其中位生存期仍为12个月。GBM在临床病理上分为原发性和继发性亚型。磷酸酶和张力蛋白同源物的突变以及下游蛋白激酶B/雷帕霉素哺乳动物靶标（mTOR）信号通路的上调在原发性GBM中常见，而在继发性GBM中较少见。虽然已经尝试对mTOR进行靶向治疗研究，但mTOR信号通路内的反馈调节可能是治疗耐药的原因。目前，雷帕霉素类似物、双靶点mTOR复合物1和2药物以及双mTOR和磷脂酰肌醇-3激酶靶向药物正在进行实验研究和临床试验。本综述将讨论这些药物在治疗GBM方面的实验潜力及其在GBM药物研发中的当前阶段。从这些药物的应用中获得的知识有助于理解GBM的发病机制以及确定后续的治疗策略。
