{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["4(9)"],"submitter":["Rutkowska A"],"pubmed_abstract":["An in-depth multiomic molecular characterization of PARP inhibitors revealed a distinct poly-pharmacology of niraparib (Zejula) mediated by its interaction with lanosterol synthase (LSS), which is not observed with other PARP inhibitors. Niraparib, in a similar way to the LSS inhibitor Ro-48-8071, induced activation of the 24,25-epoxysterol shunt pathway, which is a regulatory signaling branch of the cholesterol biosynthesis pathway. Interestingly, the combination of an LSS inhibitor with a PARP inhibitor that does not bind to LSS, such as olaparib, had an additive effect on killing cancer cells to levels comparable with niraparib as a single agent. In addition, the combination of PARP inhibitors and statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme catalyzi"],"journal":["Cancer research communications"],"pagination":["2427-2443"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11403291"],"repository":["biostudies-literature"],"pubmed_title":["Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation."],"pmcid":["PMC11403291"],"pubmed_authors":["Duempelfeld B","Braun F","Gade S","Fufezan C","Feng B","Petretich M","Alvarado D","Pocha S","Grandi P","Sweetman GMA","Remlinger K","Coleman K","Dvornikov D","Wang Z","Schofield C","Faelth-Savitski M","Jansson KH","Keles H","Curry E","Sharma G","Werner T","Reddington JP","Martinez-Segura A","Hennrich ML","Karpiak J","Bantscheff M","Rutkowska A","Stronach EA","Sevin DC","Eberl HC","Bergamini G"],"additional_accession":[]},"is_claimable":false,"name":"Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation.","description":"An in-depth multiomic molecular characterization of PARP inhibitors revealed a distinct poly-pharmacology of niraparib (Zejula) mediated by its interaction with lanosterol synthase (LSS), which is not observed with other PARP inhibitors. Niraparib, in a similar way to the LSS inhibitor Ro-48-8071, induced activation of the 24,25-epoxysterol shunt pathway, which is a regulatory signaling branch of the cholesterol biosynthesis pathway. Interestingly, the combination of an LSS inhibitor with a PARP inhibitor that does not bind to LSS, such as olaparib, had an additive effect on killing cancer cells to levels comparable with niraparib as a single agent. In addition, the combination of PARP inhibitors and statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme catalyzi","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-07-15T04:52:36.537Z","creation":"2025-04-06T16:09:31.623Z"},"accession":"S-EPMC11403291","cross_references":{"pubmed":["39028932"],"doi":["10.1158/2767-9764.CRC-23-0549"]}}