{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T02:11:37Z","timestamp":1784859097453,"version":"3.55.0"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008018","name":"Victorian Cancer Agency","doi-asserted-by":"publisher","award":["MCRF21006"],"award-info":[{"award-number":["MCRF21006"]}],"id":[{"id":"10.13039\/100008018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014538","name":"Lembaga Pengelola Dana Pendidikan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014538","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Victorian State Government - Operational Infrastructure Support"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>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 <jats:italic>BRCA1<\/jats:italic>-deficient tumours preferentially over <jats:italic>BRCA1<\/jats:italic>-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 <jats:italic>BRCA1<\/jats:italic> isogenic cell line pairs from both a triple-negative breast cancer cell line (SUM149) and adapted pre-existing non-cancerous <jats:italic>BRCA1<\/jats:italic> isogenic pair (RPE). Each cell line of the isogenic pair was transformed with its own fluorescent reporter. The two-coloured cell lines of the isogenic pair were then grown together in the same vessel to create a more competitive environment compared to when grown separately. We used four PARP inhibitors to validate the ability to detect synthetic lethality in <jats:italic>BRCA1<\/jats:italic>-deficient cancer cells. The readout of the assay was performed by counting the fluorescently coloured cells after drug treatment using flow cytometry. We observed preferential targeting of <jats:italic>BRCA1-<\/jats:italic>deficient cells, by PARPi, at relative concentrations that broadly reflect clinical dosing. Further we reveal subtle differences between PARPi resistant lines compared to <jats:italic>BRCA1-<\/jats:italic>proficient cells. Here, we demonstrate the validation and potential use of the competitive assay, which could be extended to validating novel genetic relationships and adapted for live cell imaging.<\/jats:p>","DOI":"10.1371\/journal.pone.0332860","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T17:22:57Z","timestamp":1758561777000},"page":"e0332860","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Differential PARP inhibitor responses in BRCA1-deficient and resistant cells in competitive co-culture"],"prefix":"10.1371","volume":"20","author":[{"given":"Shiella A.","family":"Soetomo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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