[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-353620-105":59,"doc-detail-353620-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","fusion-oncoproteins-orchestrate-tumorigenesis-and-sustain-malignant-progression-via-a-positive-feedback-mechanism","Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism","","Chromosomal translocations are widespread genetic events in pediatric cancers, including CNS tumors, solid tumors, and leukemias. Fusion oncoproteins generated by these events are established oncogenic drivers and can create tumor cell dependence, since loss of fusion-protein activity triggers cell death. Beyond serving as drivers, fusion proteins can form positive feedback loops with other proteins, activating oncogenic signaling, altering therapy sensitivity, and limiting single-agent fusion targeting. This review summarizes how these circuits form, their roles in initiation and progression, and emerging combination therapeutic strategies.",{"@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/fusion-oncoproteins-orchestrate-tumorigenesis-and-sustain-malignant-progression-via-a-positive-feedback-mechanism/353620/",{"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/fusion-oncoproteins-orchestrate-tumorigenesis-and-sustain-malignant-progression-via-a-positive-feedback-mechanism/353620.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What genetic events produce fusion oncoproteins in cancer?","Question",{"text":112,"@type":113},"Fusion oncoproteins arise from chromosomal translocations and related DNA rearrangements, aberrant transcription, or post-translational joining of protein fragments.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why are fusion oncoproteins considered promising targets for cancer therapy?",{"text":117,"@type":113},"Some tumor cells become dependent on fusion-protein activity, and cell death can occur when fusion proteins are depleted.",{"name":119,"@type":110,"acceptedAnswer":120},"How do positive feedback loops change treatment strategies for fusion-positive tumors?",{"text":121,"@type":113},"Positive feedback loops amplify oncogenic signals and can make single-agent targeting of the fusion protein insufficient to suppress tumor growth, supporting combination strategies instead.","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},353620,1790660188,{"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":34,"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},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","Ying et al. Cell & Bioscience (2026) 16:14 Cell & Bioscience  \n[https://doi.org/10.1186/s13578-025-01523-6](https://doi.org/10.1186/s13578-025-01523-6)  \nREVIEW Open Access  \nFusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism  \nWenwen Ying1,3,6, Xiaomin Wang1,3, Jiayi Yu1,3, Jinhu Wang1, Qiaojun He3,6, Bo Yang3,4,5,6, Yifan Chen1,3* and Meidan Ying1,2,3,4,5*  \nAbstract  \nChromosomal translocations are prevalent genetic events across multiple pediatric cancers, notably in CNS tumors, solid tumors, and leukemias. For decades, Fusion oncoproteins resulting from chromosomal translocations have been proposed as a hallmark of cancers, some of which can drive the process of cancers as the initial event of the disease. In addition, studies have shown that some tumor cells become addicted to the activity of fusion proteins, and cell death occurs when the fusion proteins are depleted. These researches suggest that fusion oncoproteins are one of the most promising targets for cancer treatment. Although fusion proteins are already recognized as critical oncogenic drivers, increasing evidence suggests that they can also form positive feedback loops with other proteins. In cancer patients, positive feedback loops have been shown to activate various oncogenic signals to drive tumor development, and influencing tumor cells’ sensitivity to different therapies. Therefore, these loops not only amplify the functions of the fusion proteins but also render single-agent targeting of the fusion protein insufficient to suppress tumor growth, highlighting the therapeutic potential of combination strategies in treating fusion-positive tumors. This review highlights the oncogenic roles of fusion protein-driven positive feedback loopsin tumor initiation and progression, outline the molecular mechanisms underlying their formation and function, and summarize emerging therapeutic strategies targeting these circuits, offering new insights into the treatment of fusion-positive cancers.  \nKeywords Fusion oncoproteins, Positive feedback loops, Cancer, Therapeutic strategies  \n*Correspondence:  \nYifan Chen[chenyifan96@zju.edu.cn](chenyifan96@zju.edu.cn)[ ](chenyifan96@zju.edu.cn)Meidan Ying [mying@zju.edu.cn](mying@zju.edu.cn)  \n1Department of Surgical Oncology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China  \n2Nanhu Brain-computer Interface Institute, Hangzhou 311100, China  \n3Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, The Children’s Hospital Zhejiang University School of Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China  \n4School of Medicine, Hangzhou City University, Hangzhou 310015, Zhejiang, China  \n5Cancer Center, Zhejiang University, Hangzhou 310058, China  \n6The Innovation Institute for Artificial Intelligence in Medicine, Zhejiang University, Hangzhou 310018, China  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. ","cbCaiprYit1INHkT","https://ap.wps.com/l/cbCaiprYit1INHkT","pdf",1887144,15,"English","# Abstract\n# Introduction\n## Fusion genes as cancer drivers\n## Feedback regulation and positive feedback in malignancy","[{\"question\":\"What genetic events produce fusion oncoproteins in cancer?\",\"answer\":\"Fusion oncoproteins arise from chromosomal translocations and related DNA rearrangements, aberrant transcription, or post-translational joining of protein fragments.\"},{\"question\":\"Why are fusion oncoproteins considered promising targets for cancer therapy?\",\"answer\":\"Some tumor cells become dependent on fusion-protein activity, and cell death can occur when fusion proteins are depleted.\"},{\"question\":\"How do positive feedback loops change treatment strategies for fusion-positive tumors?\",\"answer\":\"Positive feedback loops amplify oncogenic signals and can make single-agent targeting of the fusion protein insufficient to suppress tumor growth, supporting combination strategies instead.\"}]","Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism | PDF",1790106390,38]