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This study focuses on the c-Met receptor tyrosine kinase, often activated in lung tumors through overexpression or mutation, as a key driver of transformation and spread. An E1B55KD-deleted, replication-selective c-Met promoter-driven oncolytic adenovirus was engineered to target c-Met overexpressing cancer cells while sparing normal cells. Combining the adenovirus with rapamycin increased infectivity by elevating coxsackievirus/adenovirus receptor and αV integrin expression and triggered autophagy, suggesting a targeted therapeutic strategy.",{"@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/advancing-lung-cancer-treatment-with-combined-c-met-promoter-driven-oncolytic-adenovirus-and-rapamycin-research/329048/",{"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/advancing-lung-cancer-treatment-with-combined-c-met-promoter-driven-oncolytic-adenovirus-and-rapamycin-research/329048.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What lung cancer types does the study address, and why is it important?","Question",{"text":112,"@type":113},"The study highlights non-small cell lung cancer and small cell lung cancer, emphasizing the high mortality and morbidity that make improved treatments necessary.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the engineered oncolytic adenovirus target lung cancer cells?",{"text":117,"@type":113},"It uses an E1B55KD-deleted, replication-selective adenovirus driven by the c-Met promoter to preferentially target cells with c-Met overexpression while sparing normal cells.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the role of rapamycin in the combination therapy?",{"text":121,"@type":113},"Rapamycin, a selective mTOR inhibitor, is combined with the oncolytic adenovirus to increase infectivity by boosting receptor and integrin expression and to induce autophagy.","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},329048,1790105899,{"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":29,"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},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","cells  \nArticle  \nAdvancing Lung Cancer Treatment with Combined c-Met Promoter-Driven Oncolytic Adenovirus and Rapamycin  \nShih-Yao Chen 1,†, Chung-Teng Wang 2,3,†, Tang-Hsiu Huang 4, Jeng-Liang Tsai 3, Hao-Tien Wang 5, Yi-Ting Yen 6, Yau-Lin Tseng 6, Chao-Liang Wu 2,5,7, Jia-Ming Chang 8,9,* and Ai-Li Shiau 2,3, *  \nCitation: Chen, S.-Y.; Wang, C.-T.; Huang, T.-H.; Tsai, J.-L.; Wang, H.-T.; Yen, Y.-T.; Tseng, Y.-L.; Wu, C.-L.; Chang, J.-M.; Shiau, A.-L. Advancing Lung Cancer Treatment with Combined c-Met Promoter-Driven Oncolytic Adenovirus and Rapamycin. Cells 2024, 13, 1597 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells13181597  \nAcademic Editor: Maria Condello  \nReceived: 26 August 2024  \nRevised: 18 September 2024  \nAccepted: 20 September 2024  \nPublished: 23 September 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan; [leonlai50@gmail.com](leonlai50@gmail.com)  \n2 Tong Yuan Diabetes Center, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; [knight790105@hotmail.com](knight790105@hotmail.com) (C.-T.W.); [wumolbio@mail.ncku.edu.tw](wumolbio@mail.ncku.edu.tw) (C.-L.W.)  \n3 Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan  \n4 Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; [tangomycin0713@gmail.com](tangomycin0713@gmail.com)  \n5 Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan  \n6 Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; [b85401067@gmail.com](b85401067@gmail.com) (Y.-T.Y.); [tsengyl@mail.ncku.edu.tw](tsengyl@mail.ncku.edu.tw) (Y.-L.T.)  \n7 Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan  \n8 Thoracic Division, Department of Surgery, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan  \n9 Institute of Molecular Biology, National Chung Cheng University, Chiayi 62102, Taiwan  \n* Correspondence: [06016@cych.org.tw](06016@cych.org.tw) (J.-M.C.); [alshiau@mail.ncku.edu.tw](alshiau@mail.ncku.edu.tw) (A.-L.S.)† These authors contributed equally to this work.  \nAbstract: Lung cancer remains a formidable health challenge due to its high mortality and morbidity rates. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases, with small cell lung cancer (SCLC) accounting for the remainder. Both NSCLC and SCLC cells express receptor tyrosine kinases, which may be overexpressed or mutated in lung cancer, leading to increased activation. The c-Met receptor tyrosine kinase, crucial for cell transformation and tumor growth, invasion, and metastasis, became the focus of our study. We used an E1B55KD-deleted, replication-selective oncolytic adenovirus (Ad.What), driven by the c-Met promoter, targeting lung cancer cells with c-Met overexpression, thus sparing normal cells. Previous studies have shown the enhanced antitumor efficacy of oncolytic adenoviruses when combined with chemotherapeutic agents. We explored combining rapamycin, a selective mTOR inhibitor with promising clinical trial outcomes for various cancers, with Ad.What. This combination increased infectivity by augmenting the expression of coxsackievirus and adenovirus receptors and αV inte","cbCaijsFRwTNpYlE","https://ap.wps.com/l/cbCaijsFRwTNpYlE","pdf",10763604,14,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What lung cancer types does the study address, and why is it important?\",\"answer\":\"The study highlights non-small cell lung cancer and small cell lung cancer, emphasizing the high mortality and morbidity that make improved treatments necessary.\"},{\"question\":\"How does the engineered oncolytic adenovirus target lung cancer cells?\",\"answer\":\"It uses an E1B55KD-deleted, replication-selective adenovirus driven by the c-Met promoter to preferentially target cells with c-Met overexpression while sparing normal cells.\"},{\"question\":\"What is the role of rapamycin in the combination therapy?\",\"answer\":\"Rapamycin, a selective mTOR inhibitor, is combined with the oncolytic adenovirus to increase infectivity by boosting receptor and integrin expression and to induce autophagy.\"}]","Advancing Lung Cancer Treatment with Combined c-Met Promoter-Driven Oncolytic Adenovirus and Rapamycin - Research | PDF",1789982242,35]