DrugTargetSeqR: a genomics- and CRISPR-Cas9-based method to analyze drug targets.

TitleDrugTargetSeqR: a genomics- and CRISPR-Cas9-based method to analyze drug targets.
Publication TypeJournal Article
Year of Publication2014
AuthorsKasap C, Elemento O, Kapoor TM
JournalNat Chem Biol
Volume10
Issue8
Pagination626-8
Date Published2014 Aug
ISSN1552-4469
KeywordsAntineoplastic Agents, Benzamides, Cell Line, Tumor, Clustered Regularly Interspaced Short Palindromic Repeats, Drug Resistance, Neoplasm, Endonucleases, Epigenesis, Genetic, Genome, High-Throughput Nucleotide Sequencing, Humans, Imidazoles, Kinesin, Molecular Targeted Therapy, Mutation, Naphthoquinones, Quinazolines
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.

DOI10.1038/nchembio.1551
Alternate JournalNat. Chem. Biol.
PubMed ID24929528
PubMed Central IDPMC4123312
Grant ListR01 GM098579 / GM / NIGMS NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
GM98579 / GM / NIGMS NIH HHS / United States
T32GM007739 / GM / NIGMS NIH HHS / United States