Emerging targets for glioblastoma stem cell therapy.
Emerging targets for glioblastoma stem cell therapy.
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DOI：
10.7555/jbr.30.20150100
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发表时间：
2016-01
影响因子：
2.3
通讯作者：
Bijangi-Vishehsaraei K
中科院分区：
文献类型：
--
作者：
Safa AR;Saadatzadeh MR;Cohen-Gadol AA;Pollok KE;Bijangi-Vishehsaraei K
多形性胶质母细胞瘤（GBM），被指定为世界卫生组织（WHO）IV级星形细胞瘤，是一种致命的和治疗抗性的脑癌，由几种肿瘤细胞亚群组成，包括GBM干细胞（GSC），据信GBM干细胞（GSC）在对治疗的初始反应后有助于肿瘤复发。新出现的证据表明GBM肿瘤起源于GSC。新型疗法的开发和使用，包括调节GSC的干性、增殖和迁移的信号通路中特定蛋白质的小分子抑制剂、免疫疗法和非编码microRNA，可以提供更好的治疗GBM的方法。GSC特异性信号通路的鉴定和表征对于鉴定特异性治疗靶点是必要的，这可能导致选择性靶向GSC的更有效疗法的开发。包括mTOR、AKT、母体胚胎亮氨酸拉链激酶（MELK）、NOTCH 1和Wnt/β-连环蛋白在内的几种信号传导途径以及癌症干细胞标志物CD 133、CD 44、Oct 4、Sox 2、Nanog和ALDH 1A 1的表达维持了GSC特性。此外，发表在癌症基因组图谱（TCGA）中的数据特别证明了GBM肿瘤发生中活化的PI 3 K/AKT/mTOR通路。研究这些途径可能有助于了解GSC生物学，并导致潜在的治疗干预措施的发展，使它们对化疗和放疗更敏感。此外，最近证明GBM细胞系去分化为CSC样细胞，证明任何成功的GBM治疗剂或药物组合必须不仅消除GSC，而且消除分化的GBM细胞和整个肿瘤细胞。
Glioblastoma multiforme (GBM), designated as World Health Organization (WHO) grade IV astrocytoma, is a lethal and therapy-resistant brain cancer comprised of several tumor cell subpopulations, including GBM stem cells (GSCs) which are believed to contribute to tumor recurrence following initial response to therapies. Emerging evidence demonstrates that GBM tumors are initiated from GSCs. The development and use of novel therapies including small molecule inhibitors of specific proteins in signaling pathways that regulate stemness, proliferation and migration of GSCs, immunotherapy, and non-coding microRNAs may provide better means of treating GBM. Identification and characterization of GSC-specific signaling pathways would be necessary to identify specific therapeutic targets which may lead to the development of more efficient therapies selectively targeting GSCs. Several signaling pathways including mTOR, AKT, maternal embryonic leucine zipper kinase (MELK), NOTCH1 and Wnt/β-catenin as well as expression of cancer stem cell markers CD133, CD44, Oct4, Sox2, Nanog, and ALDH1A1 maintain GSC properties. Moreover, the data published in the Cancer Genome Atlas (TCGA) specifically demonstrated the activated PI3K/AKT/mTOR pathway in GBM tumorigenesis. Studying such pathways may help to understand GSC biology and lead to the development of potential therapeutic interventions to render them more sensitive to chemotherapy and radiation therapy. Furthemore, recent demonstration of dedifferentiation of GBM cell lines into CSC-like cells prove that any successful therapeutic agent or combination of drugs for GBM therapy must eliminate not only GSCs, but the differentiated GBM cells and the entire bulk of tumor cells.