项目驱动:通过大规模深度RNAi查发现的癌症依赖和合成致命关系汇编
E Robert McDonald1, Antoine de Weck1, Michael R Schlabach1
1Novartis Institutes for Biomedical Research, Oncology Disease Area, Basel 4002, Switzerland; Cambridge, MA 02139, USA; and Emeryville, CA 94608, USA.
Cell
|July 29, 2017
概括
这项研究通过选398个癌细胞系中的7,837个基因来绘制癌症依赖性. 这些发现为癌症治疗确定了新的治疗点,特别是瘤抑制基因丢失.
科学领域:
- 癌症生物学
- 基因组学
- 药物发现
背景情况:
- 在了解癌症突变方面取得的进步,
- 然而,与瘤抑制基因丢失相关的漏洞仍然是一个挑战.
研究的目的:
- 进行大规模的RNA干扰 (RNAi) 查以确定癌症依赖性.
- 发现各种癌症亚型的新型治疗点,特别是那些涉及瘤抑制基因丢失的点.
主要方法:
- 对398个癌细胞系进行了大规模的RNAi查.
- 使用平均每基因20个短毛RNA (shRNAs) 击倒7,837个基因的活力效应被评估.
主要成果:
- 确定癌症依赖基因的类别及其与遗传,表达和血统特征的相关性.
- 具有特征的基因相互作用网络,包括蛋白质复合体和通路合作.
- 为社区使用创建了一个全面的数据集和网络门户.
结论:
- 这项研究为发现和翻译新的癌症疗法提供了宝贵的资源.
- 已识别的依赖性为抵消瘤抑制基因丢失和改善癌症治疗策略提供了潜在的目标.
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