{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T18:22:55Z","timestamp":1780424575478,"version":"3.54.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","funder":[{"DOI":"10.13039\/100013678","name":"University of Colorado Cancer Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013678","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R25CA240122"],"award-info":[{"award-number":["1R25CA240122"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Colorado Pathology Shared Resource"},{"name":"Research Histology Division"},{"name":"Cancer Center Flow Cytometry Shared Resource"},{"name":"Animal Imaging Shared Resource","award":["P30CA046934"],"award-info":[{"award-number":["P30CA046934"]}]},{"name":"The Skin Diseases Research Cores","award":["P30AR057212"],"award-info":[{"award-number":["P30AR057212"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Atypical teratoid rhabdoid tumors (ATRT) are highly aggressive pediatric brain tumors. The available treatments rely on toxic chemotherapy and radiotherapy, which themselves can cause poor outcomes in young patients. Poly (ADP-ribose) polymerases (PARP), multifunctional enzymes which play an important role in DNA damage repair and genome stability have emerged as a new target in cancer therapy. An FDA-approved drug screen revealed that Rucaparib, a PARP inhibitor, is important for ATRT cell growth. This study aims to investigate the effect of Rucaparib treatment in ATRT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study utilized cell viability, colony formation, flow cytometry, western blot, immunofluorescence, and immunohistochemistry assays to investigate Rucaparib\u2019s effectiveness in BT16 and MAF737 ATRT cell lines. In vivo, intracranial orthotopic xenograft model of ATRT was used. BT16 cell line was transduced with a luciferase-expressing vector and injected into the cerebellum of athymic nude mice. Animals were treated with Rucaparib by oral gavaging and irradiated with 2 Gy of radiation for 3 consecutive days. Tumor growth was monitored using In Vivo Imaging System.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rucaparib treatment decreased ATRT cell growth, inhibited clonogenic potential of ATRT cells, induced cell cycle arrest and apoptosis, and led to DNA damage accumulation as shown by increased expression of \u03b3H2AX. In vivo, Rucaparib treatment decreased tumor growth, sensitized ATRT cells to radiation and significantly increased mice survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrated that Rucaparib has potential to be a new therapeutic strategy for ATRT as seen by its ability to decrease ATRT tumor growth both in vitro and in vivo.<\/jats:p><\/jats:sec>","DOI":"10.1093\/noajnl\/vdad010","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T14:18:24Z","timestamp":1676038704000},"source":"Crossref","is-referenced-by-count":2,"title":["The PARP inhibitor Rucaparib synergizes with radiation to attenuate atypical teratoid rhabdoid tumor growth"],"prefix":"10.1093","volume":"5","author":[{"given":"Irina","family":"Alimova","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Murdock","sequence":"additional","affiliation":[{"name":"Trinity College , Hartford, Connecticut , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Madhavan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breauna","family":"Brunt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujatha","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"},{"name":"The Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Vibhakar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"},{"name":"The Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children\u2019s Hospital , Aurora, Colorado , USA"},{"name":"Center for Cancer and Blood Disorders, Children\u2019s Hospital , Aurora, Colorado , USA"},{"name":"Department of Neurosurgery, University of Colorado Denver , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"issue":"1","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3171\/jns.1996.85.1.0056","article-title":"Central nervous system atypical teratoid\/rhabdoid tumors of infancy and childhood: definition of an entity","volume":"85","author":"Rorke","year":"1996","journal-title":"J Neurosurg."},{"issue":"17","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"4212","DOI":"10.1002\/cncr.27373","article-title":"Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a surveillance, epidemiology, and end results analysis","volume":"118","author":"Buscariollo","year":"2012","journal-title":"Cancer."},{"issue":"6","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1093\/neuonc\/nov264","article-title":"Atypical teratoid\/rhabdoid tumors-current concepts, advances in biology, and potential future therapies","volume":"18","author":"Fruhwald","year":"2016","journal-title":"Neuro-oncology."},{"issue":"7","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/neuonc\/noaa046","article-title":"Advancing biology-based therapeutic approaches for atypical teratoid rhabdoid tumors","volume":"22","author":"Hoffman","year":"2020","journal-title":"Neuro-oncology."},{"issue":"2","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00401-007-0243-4","article-title":"The 2007 WHO classification of tumours of the central nervous system","volume":"114","author":"Louis","year":"2007","journal-title":"Acta Neuropathol."},{"issue":"3","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1200\/JCO.2008.18.7724","article-title":"Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor","volume":"27","author":"Chi","year":"2009","journal-title":"J Clin Oncol."},{"issue":"7","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/pbc.25441","article-title":"Neurocognitive evaluation of long term survivors of atypical teratoid rhabdoid tumors (ATRT): The Canadian registry experience","volume":"62","author":"Lafay-Cousin","year":"2015","journal-title":"Pediatric Blood Cancer."},{"issue":"10","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1038\/sj.bjc.6605946","article-title":"Central nervous system penetration and enhancement of temozolomide activity in childhood medulloblastoma models by poly(ADP-ribose) polymerase inhibitor AG-014699","volume":"103","author":"Daniel","year":"2010","journal-title":"Br J Cancer."},{"issue":"5\u20136","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1101\/gad.334516.119","article-title":"PARP and PARG inhibitors in cancer treatment","volume":"34","author":"Slade","year":"2020","journal-title":"Genes Dev."},{"key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1186\/s12885-016-2656-8","article-title":"An evaluation in vitro of PARP-1 inhibitors, rucaparib and olaparib, as radiosensitisers for the treatment of neuroblastoma","volume":"16","author":"Nile","year":"2016 11","journal-title":"BMC Cancer."},{"issue":"4","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1158\/1078-0432.CCR-08-1095","article-title":"Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma","volume":"15","author":"Daniel","year":"2009","journal-title":"Clin Cancer Res."},{"issue":"3","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3892\/ijo.2022.5322","article-title":"Targeting the TP53\/MDM2 axis enhances radiation sensitivity in atypical teratoid rhabdoid tumors","volume":"60","author":"Alimova","year":"2022","journal-title":"Int J Oncol."},{"issue":"8","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1002\/ijc.31873","article-title":"Inhibition of MYC attenuates tumor cell self-renewal and promotes senescence in SMARCB1-deficient Group 2 atypical teratoid rhabdoid tumors to suppress tumor growth in vivo","volume":"144","author":"Alimova","year":"2019 15","journal-title":"Int J Cancer."},{"issue":"5","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/neuonc\/noz235","article-title":"Molecular subgrouping of atypical teratoid\/rhabdoid tumors (ATRT)\u2014a reinvestigation and current consensus","volume":"22","author":"Ho","year":"2020 15","journal-title":"Neuro-oncology."},{"issue":"4","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nrc2812","article-title":"PARP inhibition: PARP1 and beyond","volume":"10","author":"Rouleau","year":"2010","journal-title":"Nat Rev Cancer."},{"issue":"14","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"8129","DOI":"10.1093\/nar\/gkx565","article-title":"The role of poly ADP-ribosylation in the first wave of DNA damage response","volume":"45","author":"Liu","year":"2017","journal-title":"Nucleic Acids Res."},{"issue":"10","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nrm.2017.53","article-title":"The multifaceted roles of PARP1 in DNA repair and chromatin remodelling","volume":"18","author":"Ray Chaudhuri","year":"2017","journal-title":"Nat Rev Mol Cell Biol."},{"issue":"5","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1073\/pnas.0904783107","article-title":"Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130","volume":"107","author":"Hegan","year":"2010","journal-title":"Proc Natl Acad Sci USA."},{"issue":"7538","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/nature14184","article-title":"Homologous-recombination-deficient tumours are dependent on Poltheta-mediated repair","volume":"518","author":"Ceccaldi","year":"2015","journal-title":"Nature."},{"issue":"53","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"55117","DOI":"10.1074\/jbc.M404524200","article-title":"Involvement of poly(ADP-ribose) polymerase-1 and XRCC1\/DNA ligase III in an alternative route for DNA double-strand breaks rejoining","volume":"279","author":"Audebert","year":"2004","journal-title":"J Biol Chem."},{"issue":"7538","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/nature14157","article-title":"Mammalian polymerase theta promotes alternative NHEJ and suppresses recombination","volume":"518","author":"Mateos-Gomez","year":"2015","journal-title":"Nature."},{"issue":"7","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"e1001005","DOI":"10.1371\/journal.pgen.1001005","article-title":"Dual roles for DNA polymerase theta in alternative end-joining repair of double-strand breaks in Drosophila","volume":"6","author":"Chan","year":"2010","journal-title":"PLoS Genet."},{"issue":"3","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nsmb.2961","article-title":"Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase theta","volume":"22","author":"Kent","year":"2015","journal-title":"Nat Struct Mol Biol."},{"key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"109661","DOI":"10.1016\/j.biopha.2019.109661","article-title":"Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer","volume":"123","author":"Zheng","year":"2020","journal-title":"Biomed Pharmacother."},{"issue":"2","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3390\/cancers12020394","article-title":"PARP inhibitors as therapeutics: beyond modulation of PARylation","volume":"12","author":"Min","year":"2020 8","journal-title":"Cancers (Basel)."},{"issue":"3","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1158\/1535-7163.MCT-06-0552","article-title":"Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial","volume":"6","author":"Thomas","year":"2007","journal-title":"Mol Cancer Ther."},{"issue":"3","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nbt.2121","article-title":"Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors","volume":"30","author":"Wahlberg","year":"2012","journal-title":"Nat Biotechnol."},{"issue":"10106","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/S0140-6736(17)32440-6","article-title":"Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"390","author":"Coleman","year":"2017","journal-title":"Lancet."},{"issue":"5","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S1470-2045(20)30061-9","article-title":"Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial","volume":"21","author":"Ledermann","year":"2020","journal-title":"Lancet Oncol."},{"issue":"15","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1158\/1078-0432.CCR-16-2796","article-title":"A phase i\u2013ii study of the oral parp inhibitor rucaparib in patients with germline BRCA1\/2-mutated ovarian carcinoma or other solid tumors","volume":"23","author":"Kristeleit","year":"2017","journal-title":"Clin Cancer Res."},{"issue":"1","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1470-2045(16)30559-9","article-title":"Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial","volume":"18","author":"Swisher","year":"2017","journal-title":"Lancet Oncol."},{"issue":"32","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.1200\/JCO.20.01035","article-title":"Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration","volume":"38","author":"Abida","year":"2020","journal-title":"J Clin Oncol."},{"issue":"22","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1200\/JCO.21.00003","article-title":"Phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2, or PALB2","volume":"39","author":"Reiss","year":"2021","journal-title":"J Clin Oncol."},{"issue":"2","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"108240","DOI":"10.1016\/j.celrep.2020.108240","article-title":"Rucaparib treatment alters p53 oscillations in single cells to enhance DNA-double-strand-break-induced cell cycle arrest","volume":"33","author":"Hanson","year":"2020","journal-title":"Cell Rep."},{"issue":"1","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11095-014-1442-z","article-title":"Breast cancer resistance protein (BCRP\/ABCG2) and P-glycoprotein (P-GP\/ABCB1) restrict oral availability and brain accumulation of the PARP inhibitor rucaparib (AG-014699)","volume":"32","author":"Durmus","year":"2015","journal-title":"Pharm Res."},{"issue":"12","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1158\/1535-7163.MCT-15-0553","article-title":"Efficacy of PARP Inhibitor rucaparib in orthotopic glioblastoma xenografts is limited by ineffective drug penetration into the central nervous system","volume":"14","author":"Parrish","year":"2015","journal-title":"Mol Cancer Ther."},{"issue":"12","key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1158\/1535-7163.MCT-17-0365","article-title":"Restricted delivery of talazoparib across the blood-brain barrier limits the sensitizing effects of parp inhibition on temozolomide therapy in glioblastoma","volume":"16","author":"Kizilbash","year":"2017","journal-title":"Mol Cancer Ther."},{"key":"2023031114001543900_","doi-asserted-by":"crossref","first-page":"3888","DOI":"10.1158\/1538-7445.AM2019-3888","article-title":"Abstract 3888: intracranial evaluation of the in vivo pharmacokinetics, brain distribution, and efficacy of rucaparib in BRCA-mutant, triple-negative breast cancer","volume":"79","author":"Nguyen","year":"2019","journal-title":"Cancer Res."}],"container-title":["Neuro-Oncology Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/noa\/advance-article-pdf\/doi\/10.1093\/noajnl\/vdad010\/49155522\/vdad010.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/noa\/article-pdf\/5\/1\/vdad010\/49511273\/vdad010.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/noa\/article-pdf\/5\/1\/vdad010\/49511273\/vdad010.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T21:34:39Z","timestamp":1679693679000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/noa\/article\/doi\/10.1093\/noajnl\/vdad010\/7033994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/noajnl\/vdad010","relation":{},"ISSN":["2632-2498"],"issn-type":[{"value":"2632-2498","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,1]]},"published":{"date-parts":[[2023,1,1]]},"article-number":"vdad010"}}