Use of RNAi screens to uncover resistance mechanisms in cancer cells and identify synthetic lethal interactions.
Use of RNAi screens to uncover resistance mechanisms in cancer cells and identify synthetic lethal interactions.
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DOI：
10.1016/j.ddtec.2013.12.002
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发表时间：
2014-03-01
期刊：
影响因子：
--
通讯作者：
Chenchik, Alex
中科院分区：
文献类型：
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作者：
Diehl, Paul;Tedesco, Donato;Chenchik, Alex
RNAi功能缺失筛选已被证明有效地识别功能上与细胞表型有关的基因，可以设计使用不同的遗传背景或改变的环境条件来阐明遗传依赖。这些筛选方法可以被用来确定将对已批准药物的耐药性降至最低的遗传靶点，并为开发新的靶向疗法和预测联合治疗的次要靶点提供基础。特别是，四种类型的池短发夹RNA(ShRNA)筛查已被用于寻找与已知药物或其他抗癌靶点一起工作的遗传靶点，无论是以添加的方式还是以协同的方式。每种方法产生的结果都提供了推动肿瘤发生的遗传因素的有用但有限的图景。
RNAi loss-of-function screens, which have proven effective to identify genes functionally responsible for cellular phenotypes, can be designed to use different genetic backgrounds or altered environmental conditions to elucidate genetic dependencies. These sorts of screening approaches can be exploited to identify genetic targets that minimize resistance to approved drugs, and provide a basis on which to develop new targeted therapies and predict the secondary targets for combinatorial treatments. Four types of pooled short hairpin RNA (shRNA) screens, in particular, have been used to look for genetic targets that work together with known drugs or other anticancer targets, either in an additive or synergistic fashion. Each method produces results that provide a useful but limited picture of the genetic elements driving oncogenesis.