Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling
Corsello SM, Nagari RT, Spangler RD, Rossen J, Kocak M, Bryan JG, Humeidi R, Peck D, Wu X, Tang AA, Wang VM, Bender SA, Lemire E, Narayan R, Montgomery P, Ben-David U, Garvie CW, Chen Y, Rees MG, Lyons NJ, McFarland JM, Wong BT, Wang L, Dumont N, O'Hearn PJ, Stefan E, Doench JG, Harrington CN, Greulich H, Meyerson M, Vazquez F, Subramanian A, Roth JA, Bittker JA, Boehm JS, Mader CC, Tsherniak A, Golub TR
Abstract
Anti-cancer uses of non-oncology drugs have occasionally been found, but such discoveries have been serendipitous. We sought to create a public resource containing the growth inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. We used PRISM, a molecular barcoding method, to screen drugs against cell lines in pools. An unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines in a manner predictable from the cell lines’ molecular features. Our findings include compounds that killed by inducing PDE3A-SLFN12 complex formation; vanadium-containing compounds whose killing depended on the sulfate transporter SLC26A2; the alcohol dependence drug disulfiram, which killed cells with low expression of metallothioneins; and the anti-inflammatory drug tepoxalin, which killed via the multi-drug resistance protein ABCB1. The PRISM drug repurposing resource (https://depmap.org/repurposing) is a starting point to develop new oncology therapeutics, and more rarely, for potential direct clinical translation.
PRISM Repurposing dataset
The SIGMA Repurposing release contains small molecule viability datasets generated using the Broad Repurposing Library and the PRISM multiplexed cell-line viability assay.
The primary PRISM Repurposing dataset contains the results of pooled-cell line chemical-perturbation viability screens for 4,518 compounds screened against 578 or 562 cell lines.
The secondary PRISM Repurposing dataset contains the results of pooled-cell line chemical-perturbation viability screens for 1,448 compounds screened against 499 cell lines in a 8-step, 4-fold dilution, starting from 10μM.
Data processing steps are described in the README file. Further descriptions of methods will be published in an upcoming publication.
Datasets
Primary screen
Secondary screen
PRISM Screening SOP
| PRISM_SOP_Supplemental_Materials.pdf | 1 MB |
Supplementary tables
| Corsello_supplemental_tables.xlsx | 20.3 MB |
