University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA.
Neurosurg Focus. 2010 Jan;28(1):E4. doi: 10.3171/2009.10.FOCUS09210.
Glioblastoma multiforme (GBM) is a high-grade brain malignancy arising from astrocytes. Despite aggressive surgical approaches, optimized radiation therapy regimens, and the application of cytotoxic chemotherapies, the median survival of patients with GBM from time of diagnosis remains less than 15 months, having changed little in decades. Approaches that target genes and biological pathways responsible for tumorigenesis or potentiate the activity of current therapeutic modalities could improve treatment efficacy. In this regard, several genomic and proteomic strategies promise to impact significantly on the drug discovery process. High-throughput genome-wide screening with short interfering RNA (siRNA) is one strategy for systematically exploring possible therapeutically relevant targets in GBM. Statistical methods and protein-protein interaction network databases can also be applied to the screening data to explore the genes and pathways that underlie the pathological basis and development of GBM. In this study, we highlight several genome-wide siRNA screens and implement these experimental concepts in the T98G GBM cell line to uncover the genes and pathways that regulate GBM cell death and survival. These studies will ultimately influence the development of a new avenue of neurosurgical therapy by placing the drug discovery process in the context of the entire biological system.
多形性胶质母细胞瘤（GBM）是一种源自星形胶质细胞的高级别脑恶性肿瘤。尽管采用了积极的手术方法、优化的放射治疗方案和细胞毒性化疗药物的应用，GBM 患者从诊断到死亡的中位生存期仍不到 15 个月，几十年来几乎没有变化。针对导致肿瘤发生的基因和生物途径或增强现有治疗方式活性的方法可能会提高治疗效果。在这方面，几种基因组和蛋白质组策略有望对药物发现过程产生重大影响。使用短干扰 RNA（siRNA）进行高通量全基因组筛选是系统探索 GBM 中可能具有治疗意义的靶标的一种策略。统计方法和蛋白质-蛋白质相互作用网络数据库也可应用于筛选数据，以探索 GBM 病理基础和发展所涉及的基因和途径。在这项研究中，我们重点介绍了几项全基因组 siRNA 筛选，并在 T98G GBM 细胞系中实施了这些实验概念，以揭示调节 GBM 细胞死亡和存活的基因和途径。这些研究最终将通过将药物发现过程置于整个生物系统的背景下，影响神经外科治疗的新途径的发展。
