Journal
NATURE CHEMICAL BIOLOGY
Volume 10, Issue 8, Pages 626-U157Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.1551
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Funding
- Louis and Rachel Rudin Foundation
- Medical Scientist Training Program grant [NIGMS T32GM007739]
- US National Institutes of Health [GM98579]
- Starr Cancer Consortium [I6-A618]
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To identify physiological targets of drugs and bioactive small molecules, we developed an approach, named DrugTargetSeqR, which combines high-throughput sequencing, computational mutation discovery and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-based genome editing. We applied this approach to ispinesib and YM155, drugs that have undergone clinical trials as anticancer agents, and uncovered mechanisms of action and identified genetic and epigenetic mechanisms likely to cause drug resistance in human cancer cells.
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