{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Huang TT"],"funding":["Intramural NIH HHS","U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS"],"pagination":["5020-5031"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9669252"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(46)"],"pubmed_abstract":["Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a major advance in ovarian cancer, now as a treatment and as a maintenance therapy in the upfront and recurrent settings. However, patients often develop resistance to PARPis, underlining the importance of dissecting resistance mechanisms. Here, we report different dosing/timing schemes of PARPi treatment in BRCA2-mutant PEO1 cells, resulting in the simultaneous development of distinct resistance mechanisms. PARPi-resistant variants PEO1/OlaJR, established by higher initial doses and short-term PARPi treatment, develops PARPi resistance by rapidly restoring functional BRCA2 and promoting drug efflux activity. In contrast, PEO1/OlaR, developed by lower initial doses with long-term PARPi exposure, shows no regained BRCA2 function but"],"journal":["Oncogene"],"pubmed_title":["Distinct roles of treatment schemes and BRCA2 on the restoration of homologous recombination DNA repair and PARP inhibitor resistance in ovarian cancer."],"pmcid":["PMC9669252"],"funding_grant_id":["R37 CA261987","ZIA BC011525","R37CA261987-01"],"pubmed_authors":["Burkett SS","Huang TT","Yamamoto TM","Nair JR","Tandon M","Bitler BG","Lee JM","Gupta N"],"additional_accession":[]},"is_claimable":false,"name":"Distinct roles of treatment schemes and BRCA2 on the restoration of homologous recombination DNA repair and PARP inhibitor resistance in ovarian cancer.","description":"Poly (ADP-ribose) polymerase inhibitors (PARPis) represent a major advance in ovarian cancer, now as a treatment and as a maintenance therapy in the upfront and recurrent settings. However, patients often develop resistance to PARPis, underlining the importance of dissecting resistance mechanisms. Here, we report different dosing/timing schemes of PARPi treatment in BRCA2-mutant PEO1 cells, resulting in the simultaneous development of distinct resistance mechanisms. PARPi-resistant variants PEO1/OlaJR, established by higher initial doses and short-term PARPi treatment, develops PARPi resistance by rapidly restoring functional BRCA2 and promoting drug efflux activity. In contrast, PEO1/OlaR, developed by lower initial doses with long-term PARPi exposure, shows no regained BRCA2 function but","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-04T14:17:16.235Z","creation":"2025-02-19T02:23:16.94Z"},"accession":"S-EPMC9669252","cross_references":{"pubmed":["36224341"],"doi":["10.1038/s41388-022-02491-8"]}}