癌症细胞系百科全书使得抗癌药物敏感性的预测建模成为可能
Jordi Barretina1, Giordano Caponigro, Nicolas Stransky
1The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
Nature
|March 31, 2012
概括
癌症细胞系百科全书 (CCLE) 为947个癌症细胞系提供了基因组和药物敏感性数据. 该资源有助于识别药物反应的遗传预测因子,推进个性化癌症治疗.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 将癌症基因组数据转化为治疗策略是一项挑战.
- 具有基因组多样性和详细注释的临床前模型对于癌症研究至关重要.
- 癌症细胞系百科全书 (CCLE) 通过编制广泛的癌症细胞系数据来满足这一需求.
研究的目的:
- 为了描述癌症细胞系百科全书 (CCLE) 的资源.
- 识别抗癌药物敏感性的遗传,血统和基因表达基因预测因素.
- 为了证明大型的,注释的细胞系集合对于临床前药物分层的有用性.
主要方法:
- 编译了947个人类癌症细胞系的基因表达,拷贝数和测序数据.
- 在479个细胞系中获得了24种抗癌药物的药理学概况.
- 分析数据以确定药物敏感性的预测因素.
主要成果:
- 确定了细胞系和药物敏感性之间的新相关性 (例如,具有IGF1受体抑制剂的血细胞系).
- 发现的AHR表达预测了NRAS突变系中的MEK抑制剂有效性.
- 证明的SLFN11表达预测了对拓酶抑制剂的敏感性.
结论:
- 像CCLE这样的大型注释细胞系集合可以促进抗癌剂的临床前分层.
- 药物反应的遗传预测可以整合到个性化医学的临床试验设计中.
- CCLE促进了对瘤生物学和治疗可能性的理解.
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