[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-367030-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-367030-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","the-multi-kinase-inhibitor-gzd824-olverembatinib-shows-pre-clinical-efficacy-in-endometrial-cancer","The Multi-Kinase Inhibitor GZD824 (Olverembatinib) Shows Pre-Clinical Efficacy in Endometrial Cancer","","Endometrial cancer has rising mortality and limited options for certain subtypes. This study evaluates the pre-clinical efficacy of GZD824 (olverembatinib), a multi-kinase inhibitor previously explored in trials for BCR-ABL-related diseases. GZD824 was assessed across seven endometrial cancer cell lines, one normal immortalised endometrium line, and primary mesothelial and fibroblast cells. Results show inhibited proliferation in all cancer lines with enhanced sensitivity versus normal cells, reduced migration and invasion in subtype-specific models, and RNA-seq–linked pathway alterations. Findings support further therapeutic investigation in endometrial cancer.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/the-multi-kinase-inhibitor-gzd824-olverembatinib-shows-pre-clinical-efficacy-in-endometrial-cancer/367030/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/the-multi-kinase-inhibitor-gzd824-olverembatinib-shows-pre-clinical-efficacy-in-endometrial-cancer/367030.png","ImageObject",300,407,{"name":42,"@type":43},"Jiven","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-24","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main goal of this pre-clinical study?","Question",{"text":63,"@type":64},"To investigate the pre-clinical efficacy of GZD824 (olverembatinib) as a potential treatment for endometrial cancer.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was GZD824 evaluated in the study?",{"text":68,"@type":64},"Across seven endometrial cancer cell lines, one normal immortalised endometrium-derived line, and primary mesothelial and fibroblast cells from normal omentum samples, using proliferation, migration, invasion, and RNA-seq analyses.",{"name":70,"@type":61,"acceptedAnswer":71},"What outcomes did the researchers observe after GZD824 treatment?",{"text":72,"@type":64},"GZD824 inhibited proliferation in all endometrial cancer cell lines, was more effective in cancer cells than normal cells, and significantly suppressed migration and invasion in specific lines. Transcriptome changes implicated pathways including ROR1/Wnt, GCN2-ATF4, EMT, and PI3K-AKT.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},367030,1790245926,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":113},1099513958607,"https://ap-avatar.wpscdn.com/avatar/100002390cf8733938c?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778829742770036399","Cancer Medicine  \nRESEARCH ARTICLE  OPEN ACCESS   \nThe Multi-Kinase Inhibitor GZD824 (Olverembatinib) Shows Pre-Clinical Efficacy in Endometrial Cancer  \nDongli Liu1  | Dylan Glubb2 | Tracy O'Mara2  | Caroline E. Ford1  \n1Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia | 2Cancer Research Program, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia  \nCorrespondence: Caroline E. Ford ([caroline.ford@unsw.edu.au](caroline.ford@unsw.edu.au))  \nReceived: 21 February 2024 | Revised: 2 December 2024 | Accepted: 10 December 2024  \nFunding: This work was supported by the UNSW Med & Health ECAN seed grant to D.L. T.O'.M. is supported by a National Health and Medical Research Council of Australia Emerging Leader Investigator Fellowship (APP1173170) .  \nABSTRACT  \nObjective: 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 olverembatinib, is a multi-kinase inhibitor previously investigated in clinical trials for chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia as a BCR-ABL inhibitor. This study aimed to investigate the pre-clinical efficacy of GZD824 for the treatment of EC.  \nMethods: Here, we undertook pre-clinical evaluation of GZD824 in seven endometrial cancer cell lines (HEC-1-A, HEC-1-B, MFE296, RL95-2, Ishikawa, KLE and ARK-1), one normal immortalised endometrium derived cell line (E6E7hTERT) and primary mesothelial and fibroblast cells isolated from normal omentum samples.  \nResults: GZD824 inhibited the proliferation of all endometrial cancer cell lines, which were significantly more sensitive to GZD824 compared to normal cells (p = 0.030). 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 μM) of GZD824 in Ishikawa and ARK1 cells was investigated via RNA-seq, and key components of enriched pathways were investigated at the translational level. Key pathways altered included ROR1/Wnt, GCN2-ATF4, epithelial to mesenchymal transition (EMT) and PI3K-AKT.  \nConclusion: Together, these studies support further investigation of GZD824 as a potential therapeutic agent in endometrial cancer, potentially in combination with immune checkpoint inhibitors.  \n1 | Introduction  \nEndometrial cancer (EC) is the sixth most prevalent malignancy worldwide and is one of the few cancers with increasing mortality [1] . Although EC patients generally have a good outcome and are often cured by hysterectomy and bilateral salpingo-oophorectomy ± adjuvant therapy, some patients with advanced-stage or high-risk histologies receive upfront chemotherapy. Furthermore, relapse rates reach 20% in cases with the endometrioid histological subtype and 50% in non-endometrioid  \n(e.g., serous and clear cell) subtype cases [2] . Indeed, women who are diagnosed with non-endometrioid tumour subtypes or recurrent disease have a poor prognosis [2] .  \nCurrent treatment options for patients with advanced disease are limited, with only five drugs approved for EC therapy by the Food and Drug Administration (USA). The current first-line standard chemotherapy is the carboplatin-paclitaxel doublet. However, the PORTEC-3 clinical trial showed only patients harbouring TP53 mutations (mostly tumours of the serous subtype) benefited from  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.  \nCancer Medicine, 2025; 14:e70531 1 of 12  \n[https://do","cbCaibCFv4zpn6Zr","https://ap.wps.com/l/cbCaibCFv4zpn6Zr","pdf",3549101,12,"English","# Abstract\n## Objective\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What is the main goal of this pre-clinical study?\",\"answer\":\"To investigate the pre-clinical efficacy of GZD824 (olverembatinib) as a potential treatment for endometrial cancer.\"},{\"question\":\"How was GZD824 evaluated in the study?\",\"answer\":\"Across seven endometrial cancer cell lines, one normal immortalised endometrium-derived line, and primary mesothelial and fibroblast cells from normal omentum samples, using proliferation, migration, invasion, and RNA-seq analyses.\"},{\"question\":\"What outcomes did the researchers observe after GZD824 treatment?\",\"answer\":\"GZD824 inhibited proliferation in all endometrial cancer cell lines, was more effective in cancer cells than normal cells, and significantly suppressed migration and invasion in specific lines. Transcriptome changes implicated pathways including ROR1/Wnt, GCN2-ATF4, EMT, and PI3K-AKT.\"}]","The Multi-Kinase Inhibitor GZD824 (Olverembatinib) Shows Pre-Clinical Efficacy in Endometrial Cancer | PDF",1790168908]