Systematic mapping of cancer cell target dependencies using high-throughput drug screening in triple-negative breast cancer.

ABSTRACT: While high-throughput drug screening offers possibilities to profile phenotypic responses of hundreds of compounds, elucidation of the cell context-specific mechanisms of drug action requires additional analyses. To that end, we developed a computational target deconvolution pipeline that identifies the key target dependencies based on collective drug response patterns in each cell line separately. The pipeline combines quantitative drug-cell line responses with drug-target interaction networks among both intended on- and potent off-targets to identify pharmaceutically actionable and selective therapeutic targets. To demonstrate its performance, the target deconvolution pipeline was applied to 310 small molecules tested on 20 genetically and phenotypically heterogeneous triple-negative bre

SUBMITTER: Wang T 

PROVIDER: S-EPMC7720026 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature