A CRISPR-drug perturbational map for identifying compounds to combine with commonly used chemotherapeutics.

ABSTRACT: Combination chemotherapy is crucial for successfully treating cancer. However, the enormous number of possible drug combinations means discovering safe and effective combinations remains a significant challenge. To improve this process, we conduct large-scale targeted CRISPR knockout screens in drug-treated cells, creating a genetic map of druggable genes that sensitize cells to commonly used chemotherapeutics. We prioritize neuroblastoma, the most common extracranial pediatric solid tumor, where ~50% of high-risk patients do not survive. Our screen examines all druggable gene knockouts in 18 cell lines (10 neuroblastoma, 8 others) treated with 8 widely used drugs, resulting in 94,320 unique combination-cell line perturbations, which is comparable to the largest existing drug combination s

SUBMITTER: Lee HM 

PROVIDER: S-EPMC10643606 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature