Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, New York, USA.
Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York, USA.
Nat Chem Biol. 2014 Aug;10(8):626-8. doi: 10.1038/nchembio.1551. Epub 2014 Jun 15.
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.
为了鉴定药物和生物活性小分子的生理靶标，我们开发了一种名为 DrugTargetSeqR 的方法，该方法结合了高通量测序、计算突变发现和基于成簇规律间隔短回文重复（CRISPR）-Cas9 的基因组编辑。我们将这种方法应用于伊匹单抗（ispinesib）和 YM155，这两种药物都已经作为抗癌药物进行了临床试验，揭示了作用机制，并确定了可能导致人类癌细胞产生耐药性的遗传和表观遗传机制。
