Differential PARP inhibitor responses in BRCA1-deficient and resistant cells in competitive co-culture.

ABSTRACT: Synthetic lethality describes a genetic relationship where the loss of two genes results in cell death, but the loss of one of those genes does not. Drugs used for precision oncology can exploit synthetic lethal relationships; the best described are PARP inhibitors which preferentially kill BRCA1-deficient tumours preferentially over BRCA1-proficient cells. New synthetic lethal targets are often discovered using genetic screens, such as CRISPR knockout screens. Here, we present a competitive co-culture assay that can be used to analyse drugs or gene knockouts with synthetic lethal effects. We generated new BRCA1 isogenic cell line pairs from both a triple-negative breast cancer cell line (SUM149) and adapted pre-existing non-cancerous BRCA1 isogenic pair (RPE). Each cell line of the isogen

SUBMITTER: Soetomo SA 

PROVIDER: S-EPMC12453244 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature