[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-333052-105":59,"doc-detail-333052-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","emid2-is-a-novel-biotherapeutic-for-aggressive-cancers-identified-by-in-vivo-screening","EMID2 is a novel biotherapeutic for aggressive cancers identified by in vivo screening","","The study addresses why most proposed anti-cancer drugs fail: 97% collapse in clinical trials because many are discovered via cellular or in silico screens that do not reliably predict in vivo activity. An Adeno-Associated Vector secretome library (>1000 clones) was screened directly in vivo using a mouse cancer model, and the top hit, EMID2, was validated in orthotopic and genetic lung and pancreatic cancer settings. EMID2 inhibited tumor growth and metastasis, improving survival in aggressive cancers.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/emid2-is-a-novel-biotherapeutic-for-aggressive-cancers-identified-by-in-vivo-screening/333052/",{"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/emid2-is-a-novel-biotherapeutic-for-aggressive-cancers-identified-by-in-vivo-screening/333052.png","ImageObject",300,407,{"name":92,"@type":93},"Jiven","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-10","2026-09-21",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},"Why do many proposed anti-cancer drugs fail in clinical trials?","Question",{"text":112,"@type":113},"Many fail because they are identified by cellular or in silico screens that cannot predict their in vivo effects, leading to failure in most cases during clinical testing.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was EMID2 identified in this study?",{"text":117,"@type":113},"Researchers screened an Adeno-Associated Vector (AAV) secretome library directly in vivo in a mouse cancer model, then validated the first hit, EMID2, across orthotopic and genetic cancer models.",{"name":119,"@type":110,"acceptedAnswer":120},"What did EMID2 do to tumors and metastasis?",{"text":121,"@type":113},"EMID2 overexpression inhibited both tumor growth and metastatic dissemination, consistent with prolonged survival in patients whose cancers showed high EMID2 expression.","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},333052,1792393353,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"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,"preview_page_count":4},1099513958607,"https://ap-avatar.wpscdn.com/avatar/100002390cf8733938c?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778829742770036399","Cappelletto etal. Journal of Experimental & Clinical Cancer Research (2024) 43:15 [https://doi.org/10.1186/s13046-023-02942-4](https://doi.org/10.1186/s13046-023-02942-4)  \nJournal of Experimental & Clinical Cancer Research  \nRESEARCH Open Access  \nEMID2 is a novel biotherapeutic for aggressive  cancers identified by in vivo screening  \nAmbra Cappelletto1†, Edoardo Alfì1,2†, Nina Volf1, Thi Van Anh Vu1, Francesca Bortolotti5, Giulio Ciucci1, Simone Vodret1, Marco Fantuz3,4, Martina Perin 1, Andrea Colliva1, Giacomo Rozzi1, Matilde Rossi1, Giulia Ruozi5, Lorena Zentilin5, Roman Vuerich1,2, Daniele Borin6, Romano Lapasin6, Silvano Piazza7,8, Mattia Chiesa9, Daniela Lorizio9, Luca Triboli2,10, Sandeep Kumar11, Gaia Morello12, Claudio Tripodo12,13, Maurizio Pinamonti14, Giulia Maria Piperno15, Federica Benvenuti15, Alessandra Rustighi2,10, Hanjoong Jo11, Stefano Piccolo4, Giannino Del Sal2,10,16, Alessandro Carrer3,4, Mauro Giacca5,17,18 and Serena Zacchigna1,18*  \nAbstract  \nBackground New drugs to tackle the next pathway or mutation fueling cancer are constantly proposed, but 97% of them are doomed to fail in clinical trials, largely because they are identified by cellular or in silico screens that cannot predict their in vivo effect.  \nMethods We screened an Adeno-Associated Vector secretome library (> 1000 clones) directly in vivo in a mouse model of cancer and validated the therapeutic effect of the first hit, EMID2, in both orthotopic and genetic models of lung and pancreatic cancer.  \nResults EMID2 overexpression inhibited both tumor growth and metastatic dissemination, consistent with prolonged survival of patients with high levels of EMID2 expression in the most aggressive human cancers. Mechanistically, EMID2 inhibited TGFβ maturation and activation of cancer-associated fibroblasts, resulting in more elastic ECM and reduced levels ofYAP in the nuclei of cancer cells.  \nConclusion This is the first in vivo screening, precisely designed to identify proteins able to interfere with cancer cell invasiveness. EMID2 was selected as the most potent protein, in line with the emerging relevance of the tumor extracellular matrix in controlling cancer cell invasiveness and dissemination, which kills most of cancer patients. Keywords In vivo screening, Cancer, Cell invasiveness, AAV vectors, Gene therapy, Biotherapeutics  \n†Ambra Cappelletto and Edoardo Alfi contributed equally to this work.  \n*Correspondence: Serena Zacchigna[zacchign@icgeb.org](zacchign@icgeb.org)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The)[. The](http://creativecommons.org/licenses/by/4.0/. The)[ ](http://creativecommons.org/licenses/by/4.0/. The)Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data.  \nCappelletto et al. Journal of Experimental & Clinical Cancer Research  \nBackground  \nOver 90% of drug development fails despit","cbCaidrQpl0aXUrl","https://ap.wps.com/l/cbCaidrQpl0aXUrl","pdf",16418658,14,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Background and Study Rationale\n## Limitations of current screening and clinical failure rates\n## Need for targeting cancer cell invasiveness","[{\"question\":\"Why do many proposed anti-cancer drugs fail in clinical trials?\",\"answer\":\"Many fail because they are identified by cellular or in silico screens that cannot predict their in vivo effects, leading to failure in most cases during clinical testing.\"},{\"question\":\"How was EMID2 identified in this study?\",\"answer\":\"Researchers screened an Adeno-Associated Vector (AAV) secretome library directly in vivo in a mouse cancer model, then validated the first hit, EMID2, across orthotopic and genetic cancer models.\"},{\"question\":\"What did EMID2 do to tumors and metastasis?\",\"answer\":\"EMID2 overexpression inhibited both tumor growth and metastatic dissemination, consistent with prolonged survival in patients whose cancers showed high EMID2 expression.\"}]","EMID2 is a novel biotherapeutic for aggressive cancers identified by in vivo screening | PDF",1790000593,35]