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High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Channing YuAristotle M MannanGriselda Metta YvoneKenneth N RossYan-Ling ZhangMelissa A MartonBradley R TaylorAndrew CrenshawJoshua Z GouldPablo TamayoBarbara A WeirAviad TsherniakBang WongLevi A GarrawayAlykhan F ShamjiMichelle A PalmerMichael A FoleyWendy WincklerStuart L SchreiberAndrew L KungTodd R Golub
Published in: Nature biotechnology (2016)
Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo.
Keyphrases
  • high throughput
  • papillary thyroid
  • single cell
  • squamous cell
  • randomized controlled trial
  • lymph node metastasis
  • young adults
  • childhood cancer
  • cell therapy