title: DrugTargetSeqR: a genomics- and CRISPR-Cas9-based method to analyze drug targets.
abstract: 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.
authors.affiliation: Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, New York, USA.
authors.forename: Corynn
authors.initials: C
authors.lastname: Kasap
authors.affiliation: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, New York, USA.
authors.forename: Tarun M
authors.initials: TM
authors.lastname: Kapoor
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D044127:Epigenesis, Genetic; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016547:Kinesins / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation; D009285:Naphthoquinones / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007093:Imidazoles; D009285:Naphthoquinones; D011799:Quinazolines; C508757:ispinesib; D004720:Endonucleases; D016547:Kinesins; C523798:sepantronium