Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
World Neurosurg. 2019 Nov;131:252-263.e2. doi: 10.1016/j.wneu.2019.07.180. Epub 2019 Jul 31.
Glioblastoma (GBM) is the most common and deadly form of brain tumor. After standard treatment of resection, radiotherapy, and chemotherapy, the 5-year survival is <5%. In recent years, research has uncovered several potential targets within the Notch signaling pathway, which may lead to improved patient outcomes.
A literature search was performed for articles containing the terms "Glioblastoma" and "Receptors, Notch" between 2003 and July 2015. Of the 62 articles retrieved, 46 met our criteria and were included in our review. Nine articles were identified from other sources and were subsequently included, leaving 55 articles reviewed.
Of the 55 articles reviewed, 47 used established human GBM cell lines. Seventeen articles used human GBM surgical samples. Forty-five of 48 articles that assessed Notch activity showed increased expression in GBM cell lines. Targeting the Notch pathway was carried out through Notch knockdown and overexpression and targeting δ-like ligand, Jagged, γ-secretase, ADAM10, ADAM17, and Mastermindlike protein 1. Arsenic trioxide, microRNAs, and several other compounds were shown to have an effect on the Notch pathway in GBM. Notch activity in GBM was also shown to be associated with hypoxia and certain cancer-related molecular pathways such as PI3K/AKT/mTOR and ERK/MAPK. Most articles concluded that Notch activity amplifies malignant characteristics in GBM and targeting this pathway can bring about amelioration of these effects.
Recent literature suggests targeting the Notch pathway has great potential for future therapies for GBM.
胶质母细胞瘤（GBM）是最常见和最致命的脑肿瘤。在标准治疗（包括切除、放疗和化疗）后，5 年生存率<5%。近年来，研究揭示了 Notch 信号通路中的几个潜在靶点，这可能会改善患者的预后。
对 2003 年至 2015 年 7 月间含有“Glioblastoma”和“Receptors, Notch”的文章进行了文献检索。从检索到的 62 篇文章中，有 46 篇符合我们的标准并被纳入综述。此外，还从其他来源确定了 9 篇文章，最终纳入了 55 篇文章进行综述。
在综述的 55 篇文章中，有 47 篇使用了已建立的人类 GBM 细胞系。有 17 篇文章使用了人类 GBM 手术样本。在评估 Notch 活性的 48 篇文章中有 45 篇显示 GBM 细胞系中的表达增加。通过 Notch 敲低和过表达以及针对 δ 样配体、Jagged、γ-分泌酶、ADAM10、ADAM17 和 Mastermind-like protein 1 来靶向 Notch 途径。三氧化二砷、microRNAs 和其他几种化合物已被证明对 GBM 中的 Notch 途径具有影响。GBM 中的 Notch 活性也与缺氧以及 PI3K/AKT/mTOR 和 ERK/MAPK 等某些与癌症相关的分子途径有关。大多数文章的结论是，Notch 活性放大了 GBM 中的恶性特征，靶向该途径可以改善这些效应。
最近的文献表明，靶向 Notch 途径在 GBM 的未来治疗中有很大的潜力。
