To identify physiological targets of drugs and bioactive small molecules, researchers at The Rockefeller University 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. They 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.
DrugTargetSeqR: a genomics- and CRISPR-Cas9-based method to analyze drug targets
Kasap C, Elemento O, Kapoor TM. (2014) DrugTargetSeqR: a genomics- and CRISPR-Cas9-based method to analyze drug targets. Nat Chem Biol [Epub ahead of print]. [abstract]