[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-362554-105":59,"doc-detail-362554-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","retinoblastoma-unveiling-molecular-pathogenesis-and-pioneering-organoid-driven-therapeutic-innovations","Retinoblastoma: unveiling molecular pathogenesis and pioneering organoid-driven therapeutic innovations","","Retinoblastoma (RB), driven by RB1 inactivation, is the most common pediatric intraocular malignancy and remains clinically challenging due to treatment toxicity, relapse, and drug resistance. Traditional models poorly reflect human RB genetics and tumor heterogeneity, motivating advanced in vitro platforms. Human or patient-specific retinal organoids enable 3D modeling of the tumor microenvironment, mechanistic studies, and drug screening. This review covers molecular drivers, CRISPR-engineered organoid strategies, and discusses limitations and future directions including vascularization, immunocompetent systems, and multiomics integration for precision therapy.",{"@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/retinoblastoma-unveiling-molecular-pathogenesis-and-pioneering-organoid-driven-therapeutic-innovations/362554/",{"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/retinoblastoma-unveiling-molecular-pathogenesis-and-pioneering-organoid-driven-therapeutic-innovations/362554.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What makes retinoblastoma difficult to treat clinically?","Question",{"text":112,"@type":113},"Retinoblastoma is associated with treatment toxicity, relapse, and resistance, driven by RB1 inactivation and other molecular alterations.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do retinal organoids improve modeling of retinoblastoma?",{"text":117,"@type":113},"Retinal organoids derived from human pluripotent or patient-specific stem cells provide 3D tumor microenvironment modeling, preserve patient-specific genetic profiles, and support mechanistic studies and high-throughput drug screening.",{"name":119,"@type":110,"acceptedAnswer":120},"What molecular mechanisms does the review highlight in retinoblastoma pathogenesis?",{"text":121,"@type":113},"Key topics include RB1 loss, MYCN amplification, epigenetic dysregulation such as METTL3-mediated m6A, and dysregulated pathways including PI3K/AKT/mTOR and Hedgehog signaling.","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},362554,1790532918,{"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":14,"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},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Li and Jin Stem Cell Research & Therapy (2026) 17:96 [https://doi.org/10.1186/s13287-026-04951-4](https://doi.org/10.1186/s13287-026-04951-4)  \nStem Cell Research & Therapy  \nREVIEW Open Access  \nRetinoblastoma: unveiling molecular  pathogenesis and pioneering organoid-driven therapeutic innovations  \nHua Li 1*† and Chenrui Jin2†  \nAbstract  \nRetinoblastoma (RB), which is the most common pediatric intraocular malignancy driven by RB1 inactivation, presents with clinical challenges, such as treatment toxicity, relapse, and resistance. Traditional models inadequately replicate human RB genetics or tumor heterogeneity, warranting the development of advanced in vitro platforms. Retinal organoids generated from human pluripotent or patient-specific stem cells enable three-dimensional(3D) modeling of the tumor microenvironment, drug screening, and mechanistic studies. This review summarizes RB pathogenesis, including RB1 loss, MYCN amplification, epigenetic dysregulation (e. g., METTL3-mediated m6A), and dysregulated pathways (PI3K/AKT/mTOR, Hedgehog), and highlights CRISPR-engineered organoids for identifying cone precursors as tumor origins and validating therapies (CDK4/6 inhibitors and sunitinib) . Despite these advances, organoid applications are limited by high costs, variable success rates, incomplete immune/vascular mimicry, and limited scalability. Current microfluidic systems partially address vascularization but lack functional perfusion. Future efforts should integrate multiomics, refine vascularization via 3D bioprinting, and develop immunocompetent models to address the disparity between preclinical research and clinical application. Organoid technology has the potential to advance personalized therapies and ultimately enhance the survival and quality of life of patients with RB worldwide.  \nKeywords Retinoblastoma, Organoid model, Signaling pathway, Precision medicine  \n†Hua Li and Chenrui Jin contributed equally to this work.  \n*Correspondence:  \nHua Li  \n[2022220507@stu.cqmu.edu.cn](2022220507@stu.cqmu.edu.cn)  \n1Department of Ophthalmology, The Affiliated Yongchuan Hospital of Chongqing Medical University, Yongchuan District, Chongqing 402160, People’s Republic of China  \n2Optometry and Ophthalmology Medicine, The Fifth Clinical College of Chongqing Medical University, Shapingba District, Chongqing 400000, People’s Republic of China  \nBackground  \nRetinoblastoma (RB), which is the most common intraocular malignancy in children, arises primarily from biallelic inactivation of the RB1 tumor suppressor gene and has an incidence of approximately 1 in 15,000–20,000 live births worldwide, representing approximately 8,000 newly diagnosed cases annually [1]. The predominant clinical manifestations of RB are leukocoria and strabismus, and leukocoria constitutes the presenting symptom in approximately 60% of cases [2]. It can metastasize or invade other tissues, poses a significant threat to vision and is life-threatening. Despite advancements in treatments, such as chemotherapy, radiotherapy and enucleation, challenges such as toxicity, relapse, and resistance  \n© The Author(s) 2026. 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 permitte","cbCaihLrVhLskXEA","https://ap.wps.com/l/cbCaihLrVhLskXEA","pdf",1581749,13,"English","# Abstract\n## Background\n## Clinical feature\n## Molecular pathogenesis and organoid applications","[{\"question\":\"What makes retinoblastoma difficult to treat clinically?\",\"answer\":\"Retinoblastoma is associated with treatment toxicity, relapse, and resistance, driven by RB1 inactivation and other molecular alterations.\"},{\"question\":\"How do retinal organoids improve modeling of retinoblastoma?\",\"answer\":\"Retinal organoids derived from human pluripotent or patient-specific stem cells provide 3D tumor microenvironment modeling, preserve patient-specific genetic profiles, and support mechanistic studies and high-throughput drug screening.\"},{\"question\":\"What molecular mechanisms does the review highlight in retinoblastoma pathogenesis?\",\"answer\":\"Key topics include RB1 loss, MYCN amplification, epigenetic dysregulation such as METTL3-mediated m6A, and dysregulated pathways including PI3K/AKT/mTOR and Hedgehog signaling.\"}]","Retinoblastoma: unveiling molecular pathogenesis and pioneering organoid-driven therapeutic innovations | PDF",1790148251,33]