Identification of Intrinsic Drug Resistance and Its Biomarkers in High-Throughput Pharmacogenomic and CRISPR Screens.

ABSTRACT: High-throughput drug screens in cancer cell lines test compounds at low concentrations, thereby enabling the identification of drug-sensitivity biomarkers, while resistance biomarkers remain underexplored. Dissecting meaningful drug responses at high concentrations is challenging due to cytotoxicity, i.e., off-target effects, thus limiting resistance biomarker discovery to frequently mutated cancer genes. To address this, we interrogate subpopulations carrying sensitivity biomarkers and consecutively investigate unexpectedly resistant (UNRES) cell lines for unique genetic alterations that may drive resistance. By analyzing the GDSC and CTRP datasets, we find 53 and 35 UNRES cases, respectively. For 24 and 28 of them, we highlight putative resistance biomarkers. We find clinically relevant

SUBMITTER: Ayestaran I 

PROVIDER: S-EPMC7660407 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature