{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:35:12Z","timestamp":1784230512996,"version":"3.55.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1173170"],"award-info":[{"award-number":["APP1173170"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Endometrial cancer is one of the few cancers for which mortality is still increasing. A lack of treatment options remains a major challenge, particularly for some subtypes of the disease. GZD824, also known as\n                      <jats:italic>olverembatinib<\/jats:italic>\n                      , is a multi\u2010kinase inhibitor previously investigated in clinical trials for chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia as a BCR\u2010ABL inhibitor. This study aimed to investigate the pre\u2010clinical efficacy of GZD824 for the treatment of EC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we undertook pre\u2010clinical evaluation of GZD824 in seven endometrial cancer cell lines (HEC\u20101\u2010A, HEC\u20101\u2010B, MFE296, RL95\u20102, Ishikawa, KLE and ARK\u20101), one normal immortalised endometrium derived cell line (E6E7hTERT) and primary mesothelial and fibroblast cells isolated from normal omentum samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GZD824 inhibited the proliferation of all endometrial cancer cell lines, which were significantly more sensitive to GZD824 compared to normal cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.030). GZD824 significantly inhibited migration in Ishikawa (endometrioid) and ARK1 (serous) endometrial cancer cell lines and significantly inhibited invasion in the ARK1 cells. Whole transcriptome regulation following two doses (0.1 and 1\u2009\u03bcM) of GZD824 in Ishikawa and ARK1 cells was investigated via RNA\u2010seq, and key components of enriched pathways were investigated at the translational level. Key pathways altered included ROR1\/Wnt, GCN2\u2010ATF4, epithelial to mesenchymal transition (EMT) and PI3K\u2010AKT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these studies support further investigation of GZD824 as a potential therapeutic agent in endometrial cancer, potentially in combination with immune checkpoint inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70531","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T06:00:37Z","timestamp":1735538437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Multi\u2010Kinase Inhibitor GZD824 (Olverembatinib) Shows Pre\u2010Clinical Efficacy in Endometrial Cancer"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1755-8516","authenticated-orcid":false,"given":"Dongli","family":"Liu","sequence":"first","affiliation":[{"name":"Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Clinical Medicine, Faculty of Medicine &amp; Health University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"Glubb","sequence":"additional","affiliation":[{"name":"Cancer Research Program QIMR Berghofer Medical Research Institute  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5436-3232","authenticated-orcid":false,"given":"Tracy","family":"O'Mara","sequence":"additional","affiliation":[{"name":"Cancer Research Program QIMR Berghofer Medical Research Institute  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline E.","family":"Ford","sequence":"additional","affiliation":[{"name":"Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Clinical Medicine, Faculty of Medicine &amp; Health University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djx214"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00130-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00549"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2302312"},{"key":"e_1_2_8_6_1","unstructured":"U. S. F. D.Administration \u201cFDA Approves Dostarlimab\u2010Gxly With Chemotherapy for Endometrial Cancer \u201d2023 https:\/\/www.fda.gov\/drugs\/drug\u2010approvals\u2010and\u2010databases\/fda\u2010approves\u2010dostarlimab\u2010gxly\u2010chemotherapy\u2010endometrial\u2010cancer#:~:text=On%20July%2031%2C%202023%2C%20the by%20an%20FDA%2Dapproved%20test%2C."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2108330"},{"key":"e_1_2_8_8_1","unstructured":"U. S. F. D.Administration \u201cFDA Grants Regular Approval to Pembrolizumab and Lenvatinib for Advanced Endometrial Carcinoma \u201d2021 https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010grants\u2010regular\u2010approval\u2010pembrolizumab\u2010and\u2010lenvatinib\u2010advanced\u2010endometrial\u2010carcinoma."},{"issue":"1","key":"e_1_2_8_9_1","first-page":"1","article-title":"ROR1 Is Upregulated in Endometrial Cancer and Represents a Novel Therapeutic Target","volume":"10","author":"Liu D.","year":"2020","journal-title":"Scientific Reports"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2018.01.025"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.06.018"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.368"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003276"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04301-6"},{"key":"e_1_2_8_15_1","unstructured":"U. S. F. D.Administration \u201cPonatinib (Marketed as Iclusig) Information \u201d2015 https:\/\/www.fda.gov\/drugs\/postmarket\u2010drug\u2010safety\u2010information\u2010patients\u2010and\u2010providers\/ponatinib\u2010marketed\u2010iclusig\u2010informaton."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.09.028"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0450"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2131-z"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyab040"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01252-0"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-119142"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-124295"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/molpharm.120.000070"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05427-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11101440"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02745-3"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1TB01837J"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.2144\/000113083"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13030383"},{"key":"e_1_2_8_30_1","unstructured":"S.Andrews \u201cFastQC: A Quality Control Tool for High Throughput Sequence Data \u201d2010 http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw354"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz114"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5643"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-0774.2002.tb00103.x"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02618053"},{"key":"e_1_2_8_41_1","first-page":"231","article-title":"Role of In\u00a0Vitro Cell System in the Study on Hormone and Endometrial Carcinoma","volume":"58","author":"Kuramoto H.","year":"1989","journal-title":"Obstetrics and Gynecology Therapy"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605448"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910570121"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-8258(84)90080-5"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1112253"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-100814-125315"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2841"},{"issue":"4","key":"e_1_2_8_48_1","first-page":"238","article-title":"Neuronal Guidance Genes in Health and Diseases","volume":"14","author":"Yuasa\u2010Kawada J.","year":"2023","journal-title":"Protein & Cell"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.060"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11101440"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0113-1"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83535"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.06.036"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2013.2944"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2011.12.033"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2014.07.005"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2010.01829.x"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.5894"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2021.12.031"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-1564"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2023-5071"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-15-0218"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2022.10.024"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.70531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T06:10:26Z","timestamp":1764742226000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.70531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,30]]},"references-count":62,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/cam4.70531"],"URL":"https:\/\/doi.org\/10.1002\/cam4.70531","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,30]]},"assertion":[{"value":"2024-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70531"}}