Harnessing synthetic lethal interactions in anticancer drug discovery.
Harnessing synthetic lethal interactions in anticancer drug discovery.
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DOI：
10.1038/nrd3374
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发表时间：
2011-05
影响因子：
120.1
通讯作者：
Giaccia, Amato J.
中科院分区：
文献类型：
--
作者：
Chan, Denise A.;Giaccia, Amato J.
可以通过靶向治疗利用的肿瘤的独特特征是当前癌症研究的关键焦点。一种这样的方法被称为合成致死性筛选，其涉及搜索两种突变的遗传相互作用，其中任一突变单独存在对细胞活力没有影响，但两种突变的组合导致细胞死亡。因此，在癌细胞中存在这些突变之一而不是在正常细胞中存在，可以通过模拟靶向治疗的第二个基因突变的作用来创造选择性杀死癌细胞的机会。在这里，我们总结了可用于识别抗癌药物发现的合成致死相互作用的策略，描述了目前正在研究的靶向抗癌疗法的临床前和临床研究中的这种相互作用的例子，并讨论了实现这种疗法的全部潜力的挑战。
Unique features of tumours that can be exploited by targeted therapies are a key focus of current cancer research. One such approach is known as synthetic lethality screening, which involves searching for genetic interactions of two mutations whereby the presence of either mutation alone has no effect on cell viability but the combination of the two mutations results in cell death. The presence of one of these mutations in cancer cells but not in normal cells can therefore create opportunities to selectively kill cancer cells by mimicking the effect of the second genetic mutation with targeted therapy. Here, we summarize strategies that can be used to identify synthetic lethal interactions for anticancer drug discovery, describe examples of such interactions that are currently being investigated in preclinical and clinical studies of targeted anticancer therapies, and discuss the challenges of realizing the full potential of such therapies.
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基于肿瘤微环境的癌细胞杀伤的背景综合致死率。
影响因子：
11.2
作者：
Chan N;Pires IM;Bencokova Z;Coackley C;Luoto KR;Bhogal N;Lakshman M;Gottipati P;Oliver FJ;Helleday T;Hammond EM;Bristow RG
通讯作者：
Bristow RG
影响因子：
5.3
作者：
Bindra, RS;Schaffer, PJ;Glazer, PM
通讯作者：
Glazer, PM
影响因子：
158.5
作者：
Druker, Brian J.;Guilhot, Francois;Larson, Richard A.
通讯作者：
Larson, Richard A.
影响因子：
64.8
作者：
Brummelkamp, TR;Nijman, SMB;Bernards, R
通讯作者：
Bernards, R
影响因子：
4.8
作者：
Bhattacharyya, A;Ear, US;Bishop, DK
通讯作者：
Bishop, DK