Vivian L Smith Department of Neurosurgery, University of Texas Medical School at Houston, 6431 Fannin Street, MSE R266, Houston, TX 77030, USA.
Curr Mol Med. 2013 Mar;13(3):352-7.
Glioblastoma (GBM) is a highly malignant primary brain tumor known for its invasiveness and aggressive resistance to standard treatment. It is currently the most common primary brain tumor which is associated with a high mortality rate. Tumor initiating cells (TICs) are a subpopulation of GBM stem cells which are capable of self-renewal and apoptotic resistance, and are thought to account for GBMs aggressive nature. Recent efforts have focused on therapies which target key intracellular apoptotic pathways which may confer tumor resistance, such as Akt, p53, Bcl-2 family proteins, caspase family proteases, and more recently microRNAs. Research into microRNA's role in GBM has shown that microRNAs play a key regulatory role in the GBM apoptotic pathway, making it a potential therapeutic target. In this review we summarized the molecular mechanisms involved in the signaling pathways of human GBM TIC apoptosis and microRNAs, the contemporary treatments involving different members of the signaling cascade, and the future direction of GBM treatment strategies.
胶质母细胞瘤(GBM)是一种高度恶性的原发性脑肿瘤,以其侵袭性和对标准治疗的强烈抵抗而闻名。它是目前最常见的原发性脑肿瘤,死亡率很高。肿瘤起始细胞(TICs)是 GBM 干细胞的一个亚群,能够自我更新和抗凋亡,被认为是 GBM 侵袭性的原因。最近的研究集中在针对关键细胞内凋亡途径的治疗方法上,这些途径可能导致肿瘤耐药,如 Akt、p53、Bcl-2 家族蛋白、半胱天冬酶家族蛋白酶,以及最近的 microRNAs。对 microRNA 在 GBM 中的作用的研究表明,microRNAs 在 GBM 凋亡途径中发挥关键的调节作用,使其成为一个潜在的治疗靶点。在这篇综述中,我们总结了涉及人类 GBM TIC 凋亡和 microRNAs 的信号通路的分子机制、涉及信号级联不同成员的当代治疗方法,以及 GBM 治疗策略的未来方向。