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In cancer, however, cell-cell fusion disrupts homeostasis and increases heterogeneity by enabling fusion between cancer and normal host cells, which supports growth, metastasis, and immune escape. Fusion among cancer cells generates polyploid giant cancer cells (PGCCs), considered cancer stem-cell roots of metastasis, treatment resistance, and recurrence. The emergence of fusion-informed detection and targeted therapies offers potential clinical promise supported by advances in cell culture.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-influence-of-cell-cell-fusion-on-cancer-heterogeneity-and-its-promise-for-targeted-treatments/358325/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-influence-of-cell-cell-fusion-on-cancer-heterogeneity-and-its-promise-for-targeted-treatments/358325.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does cell-cell fusion normally contribute to organism development?","Question",{"text":112,"@type":113},"In physiological conditions, cell-cell fusion supports homeostasis and processes such as zygote formation, placental development, muscle growth, and macrophage formation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is cell-cell fusion associated with cancer progression?",{"text":117,"@type":113},"In cancer, cell-cell fusion destabilizes homeostasis and enhances heterogeneity, including fusion between cancer cells and normal host cells that promotes growth, metastasis, and immune escape.",{"name":119,"@type":110,"acceptedAnswer":120},"What are polyploid giant cancer cells (PGCCs) and why are they important?",{"text":121,"@type":113},"PGCCs are polyploid, cancer stem cell–like cells linked to metastasis, chemoradiotherapy resistance, and recurrence, and their presence drives cancer evolution.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},358325,1790562759,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","Cellular Oncology (2026) 49:22  \n[https://doi.org/10.1007/s13402-025-01](https://doi.org/10.1007/s13402-025-01)153-7  \nREVIEW  \nThe influence of cell-cell fusion on cancer heterogeneity and its promise for targeted treatments  \nKairui Liu1 · Jialong Shi2 · Jiayue Liu2 · Yue Zhang5 · Jingjing Liang1 · Jing Xu3 · Shuo Chen4 · Shiwu Zhang5  \nReceived: 24 June 2025 / Accepted: 3 October 2025 © The Author(s) 2026  \nAbstract  \nCell-cell fusion is a common cellular process that occurs in nature. In the physiological environment, cell-cell fusion plays a crucial role in the establishment of homeostasis and the normal development of an organism. Normal cell-cell fusion is related to zygote formation, placental development, muscle growth, and macrophage formation. However, in cancer, cell-cell fusion destabilizes homeostasis and enhances cancer heterogeneity. The fusion of cancer and normal host cells, such as mesenchymal stem cells or white blood cells, promotes cancer growth, metastasis, and immune escape. On the other hand, fusion of cancer cells with each other leads directly to the formation of polyploid giant cancer cells (PGCCs) . PGCCs are cancer stem cells considered the root cause of cancer metastasis, chemoradiotherapy resistance and recurrence. The presence of PGCCs significantly promotes the evolution of cancer. Clinical detection and targeted therapies based on cell-cell fusion have rapidly emerged with advancements in cell culture technology, which may bring hope to the treatment of cancer patients.  \nKairui Liu, Jialong Shi and Jiayue Liu contributed equally to this work.  \n􀀍 Shiwu Zhang [zhangshiwu666@aliyun.com](zhangshiwu666@aliyun.com)[ ](zhangshiwu666@aliyun.com)Kairui Liu [LKR1141743622@163.com](LKR1141743622@163.com)[ ](LKR1141743622@163.com)Jialong Shi [2118865539@qq.com](2118865539@qq.com)  \nJiayue Liu  \n[13231265993@163.com](13231265993@163.com)[ ](13231265993@163.com)Yue Zhang [zhangyue0114@yeah.net](zhangyue0114@yeah.net)[ ](zhangyue0114@yeah.net)Jingjing Liang [17831961692@163.com](17831961692@163.com)  \nJing Xu  \n[xujingdoc@126.com](xujingdoc@126.com)  \nShuo Chen  \n[chenshuo19801106@126.com](chenshuo19801106@126.com)  \n1 Tianjin Union Medical Center, Tianjin Medical University, Tianjin 300121, P. R. China  \n2 Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China  \n3 Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, P. R. China  \n4 Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P. R. China  \n5 Department of Pathology, Tianjin Union Medical Center, Tianjin 300071, P. R. China  \n1 3  \nGraphical Abstract  \nKeywords Cell-cell fusion · Polyploid giant cancer cells · Epithelial-mesenchymal transition · Fusion-related proteins  \n1 Introduction  \nCell-cell fusion occurs widely in organisms, from unicellular organisms such as yeast to multicellular mammals, and is fundamental to the birth and continuation of life [1–3] . Homotypic fusion of cells of the same lineage produces syncytia. The fusion of cells from different lineages results in heterokaryon formation, which is called heterotypic fusion [4, 5] . Cell-cell fusion in the physiological state proceeds in an intrinsic and inherent manner [6] . For example, sperm-oocyte heterotypic fusion during fertilization forms zygotes [7] . Chorionic trophoblast cell fusion forms syncytiotrophoblasts, which contribute to placental formation [8] . Homotypic fusion of muscle cells promotes muscle regeneration and development [9] . Under pathological conditions,  \ncell-cell fusion requires stimulation of the extracellular environment [6] . Mononuclear macrophage lines with a high homotypic fusion capacity form Langhans giant cells and foreign body giant cells in response to infections by pathogens such as Mycobacterium tuberculosis and foreign body reactions [10, 11] . Oncogenic viruses often cause the generation of fusion cells with chromosomal instability and inhibit their ap","cbCaifxW6ZSFvdIS","https://ap.wps.com/l/cbCaifxW6ZSFvdIS","pdf",6621349,22,"English","# Abstract\n# Keywords\n# Introduction","[{\"question\":\"How does cell-cell fusion normally contribute to organism development?\",\"answer\":\"In physiological conditions, cell-cell fusion supports homeostasis and processes such as zygote formation, placental development, muscle growth, and macrophage formation.\"},{\"question\":\"Why is cell-cell fusion associated with cancer progression?\",\"answer\":\"In cancer, cell-cell fusion destabilizes homeostasis and enhances heterogeneity, including fusion between cancer cells and normal host cells that promotes growth, metastasis, and immune escape.\"},{\"question\":\"What are polyploid giant cancer cells (PGCCs) and why are they important?\",\"answer\":\"PGCCs are polyploid, cancer stem cell–like cells linked to metastasis, chemoradiotherapy resistance, and recurrence, and their presence drives cancer evolution.\"}]","The influence of cell-cell fusion on cancer heterogeneity and its promise for targeted treatments | PDF",1790133682,55]