{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:40:29Z","timestamp":1777876829260,"version":"3.51.4"},"reference-count":69,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100025520","name":"Medical Research Future Fund","doi-asserted-by":"publisher","award":["APP1199620"],"award-info":[{"award-number":["APP1199620"]}],"id":[{"id":"10.13039\/501100025520","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Drug repurposing has emerged as an effective strategy to accelerate drug discovery. Using the pipeline established from a large collaborative drug repurposing project focused on high-grade serous ovarian cancer (HGSOC), we identified ivacaftor, an FDA-approved cystic fibrosis medication, as a drug candidate predicted to interact with the receptor tyrosine kinase-like orphan receptor 1 (ROR1) which we have previously demonstrated as a therapeutic target in ovarian cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>This study aimed to provide preclinical evidence supporting the potential repurposing of ivacaftor for HGSOC treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Ivacaftor was tested in 2D and 3D preclinical models as well as patient-derived organoid models in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Dose\u2013response analysis was undertaken in ROR1 expressing HGSOC cell lines OVCAR4, KURAMOCHI, COV362 and COV318 in both 2D adherent and 3D bioprinted formats. Real-time live\/dead and apoptosis cell staining were performed over a 72\u2009h period using the IncuCyte live cell imaging platform. Flow cytometry was used to assess apoptosis, DNA damage and cell proliferation following treatment with either 15\u2009\u00b5M ivacaftor or 30\u2009\u00b5M carboplatin at 24, 48 and 72\u2009h. Additionally, ROR1-expressing HGSOC patient-derived organoids (OC029, OC043 and OC058) underwent ivacaftor dose\u2013response analysis. Cell apoptosis following 15\u2009\u00b5M ivacaftor treatment was measured in real-time using an Annexin V assay in two additional organoid models (OC062 and OC075). Finally, the mechanisms associated with response to ivacaftor were explored in HGSOC cell lines through Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The IC50 for ivacaftor ranged from 6.5 to 13.2\u2009\u00b5M in 2D cultures and 11.6 to 18.2\u2009\u00b5M in 3D cultures. Treatment with 10 and 15\u2009\u00b5M ivacaftor resulted in significantly increased cell death and reduced live cell counts compared to the vehicle control over 72\u2009h. Organoids displayed IC50 values between 11.2 and 14.1\u2009\u00b5M. Ivacaftor treatment induced apoptosis in organoids, with no significant impact on DNA damage or cell cycle in HGSOC cells. ROR1 signalling associated oncogenic pathways including the BMI-1 and the PI3K\/AKT pathways were modulated following ivacaftor treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In summary, ivacaftor demonstrated significant anti-tumour potential in preclinical HGSOC models, supporting its further investigation as a repurposed therapy for ovarian cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359251409010","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T08:51:55Z","timestamp":1767343915000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing of ivacaftor shows potential to treat ROR1 expressing high-grade serous ovarian cancer"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1755-8516","authenticated-orcid":false,"given":"Dongli","family":"Liu","sequence":"first","affiliation":[{"name":"Gynaecological Cancer Research Group, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Wong-Brown","sequence":"additional","affiliation":[{"name":"Equity in Health and Wellbeing Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia"},{"name":"School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhana Amy","family":"Sarker","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bayley","family":"Matthews","sequence":"additional","affiliation":[{"name":"Equity in Health and Wellbeing Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia"},{"name":"School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Morrison","sequence":"additional","affiliation":[{"name":"Equity in Health and Wellbeing Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia"},{"name":"School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristie-Ann","family":"Dickson","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2308-0256","authenticated-orcid":false,"given":"Amani","family":"Alghalayini","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Stojanova","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology, St Vincent\u2019s Hospital Sydney, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"King Man","family":"Wan","sequence":"additional","affiliation":[{"name":"Gynaecological Oncology Department, Royal Hospital for Women, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Duggan","sequence":"additional","affiliation":[{"name":"Gynaecological Oncology Department, Royal Hospital for Women, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Loo","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, NSW Health Pathology, Prince of Wales Hospital, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gill","family":"Stannard","sequence":"additional","affiliation":[{"name":"Equity in Health and Wellbeing Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elyse","family":"Powell","sequence":"additional","affiliation":[{"name":"Gynaecological Cancer Research Group, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Hodder","sequence":"additional","affiliation":[{"name":"Gynaecological Cancer Research Group, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Barlow","sequence":"additional","affiliation":[{"name":"Gynaecological Cancer Research Group, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5899-4931","authenticated-orcid":false,"given":"Deborah J.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline E.","family":"Ford","sequence":"additional","affiliation":[{"name":"Gynaecological Cancer Research Group, Lowy Cancer Research Centre and School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikola A.","family":"Bowden","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Equity in Health and Wellbeing Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-024-00881-3"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2017.10.032"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101055"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2020.07.097"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-04-712562"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816262116"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419599111"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5643"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014760"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2083"},{"issue":"3","key":"e_1_3_4_12_2","article-title":"ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth","volume":"7","author":"Zhang S","year":"2012","unstructured":"Zhang S, Chen L, Cui B, et al. ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth. PLoS One 2012; 7(3): e31127.","journal-title":"PLoS One"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22559"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22426"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2016.32"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58864-0"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83535"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.70531"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.013"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080812"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.05.018"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.7556"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/17588359251332471"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-2172"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15041148"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.05.016"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.37349\/etat.2023.00192"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20943823"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci800110p"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4306"},{"issue":"8","key":"e_1_3_4_31_2","first-page":"1197","article-title":"Biological characterization including sensitivity to mitomycin C of cultured human ovarian cancers (author\u2019s transl)","volume":"33","author":"Motoyama T.","year":"1981","unstructured":"Motoyama T. Biological characterization including sensitivity to mitomycin C of cultured human ovarian cancers (author\u2019s transl). Nihon Sanka Fujinka Gakkai Zasshi 1981; 33(8): 1197\u20131204.","journal-title":"Nihon Sanka Fujinka Gakkai Zasshi"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1995.1097"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910530415"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1989.108"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3126"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12645"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11003"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.202100125"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1039\/D2BM00651K"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omton.2024.200911"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70924-z"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198100221-00010"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1992.tb04041.x"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05854-7"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.88659.3"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602811"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-3083"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.128.2.167"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2006.09.006"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10010142"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/534314a"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2023.103726"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d741"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.168"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-023-00168-9"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805143382001"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.1166"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10071527"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00169.2005"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201301-0153OC"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105185"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14081674"},{"key":"e_1_3_4_63_2","author":"Vertex Pharmaceuticals Australia Pty Ltd. Kalydeco (ivacaftor) Product Information","year":"2024","unstructured":"Vertex Pharmaceuticals Australia Pty Ltd. Kalydeco (ivacaftor) Product Information. Therapeutic Goods Administration (AusPAR Attachment) 2024.","journal-title":"Therapeutic Goods Administration (AusPAR Attachment)"},{"key":"e_1_3_4_64_2","unstructured":"Food and Drug Administration Center for Drug Evaluation and Research. Center for drug evaluation and research. Application number: 203188Orig1s000 2012."},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16040741"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.678209"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7053"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251910360"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.203"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02998-6"}],"container-title":["Therapeutic Advances in Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17588359251409010","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17588359251409010","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17588359251409010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:33:58Z","timestamp":1777588438000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17588359251409010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":69,"alternative-id":["10.1177\/17588359251409010"],"URL":"https:\/\/doi.org\/10.1177\/17588359251409010","relation":{},"ISSN":["1758-8359","1758-8359"],"issn-type":[{"value":"1758-8359","type":"print"},{"value":"1758-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"article-number":"17588359251409010"}}