Transcriptional profiling of LS1034 cells treated with tepoxalin

LS1034 colorectal cancer cells were treated with DMSO vehicle control or 12 uM tepoxalin for 6 hours. Anti-cancer uses of non-oncology drugs have been found on occasion, but such discoveries have been serendipitous and rare. To fully discover activity against multiple tumor types, resource-intensive screening across hundreds of cancer cell lines is needed. We sought to create a public resource containing the growth inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. To accomplish this, we used PRISM, which involves the molecular barcoding of each cell line, followed by pooling of the barcoded lines. Relative barcode abundance following drug treatment versus controls thus reflects cell viability following drug treatment. We found that an unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines. Moreover, the killing activity of the majority of these drugs was predictable based on the molecular features of the cell lines. Mechanistic follow-up of several of these compounds revealed novel mechanisms. These results illustrate the potential of the PRISM drug repurposing resource as a starting point for new oncology therapeutic development. Overall design: 6 samples total: LS1034 cells treated with tepoxalin for 6 hours (triplicate) or DMSO vehicle control (triplicate)