[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-341277-105":59,"doc-detail-341277-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","targeting-the-core-program-of-metastasis-with-a-novel-drug-combination","Targeting the core program of metastasis with a novel drug combination","","Metastases follow a conserved gene-expression core that drives tissue remodeling and vascularization, disrupts ion homeostasis, promotes oxidative metabolism, and suppresses extracellular-matrix interactions. This shared program differentiates metastases from both the originating primary tumors and the destination host tissues, making its gene products actionable targets for therapy. The study tests inhibitors against three non-ECM components, showing additive or synergistic effects in combination treatments that markedly reduce disseminated foci in mouse cancer models.",{"@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/targeting-the-core-program-of-metastasis-with-a-novel-drug-combination/341277/",{"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/targeting-the-core-program-of-metastasis-with-a-novel-drug-combination/341277.png","ImageObject",300,407,{"name":92,"@type":93},"Violet","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",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 is the central idea behind targeting metastasis in this study?","Question",{"text":112,"@type":113},"Metastases share a conserved core gene-expression program that controls tissue remodeling/vascularization, ion homeostasis, oxidative metabolism, and extracellular-matrix interaction silencing. Targeting the gene products underlying this program is proposed as an anti-metastasis strategy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were the drug candidates evaluated in the experiments?",{"text":117,"@type":113},"Inhibitors were tested against the three components other than extracellular-matrix interaction silencing. The study assessed effects on soft-agar colony formation in breast and pancreatic cancer cell lines and then evaluated combinations in two mouse models.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the key findings for drug combinations in vivo?",{"text":121,"@type":113},"Across two mouse models, combination treatment—given either immediately to prevent metastasis formation or after a delay to suppress established metastases—dramatically reduced the occurrence of disseminated foci. Effects were additive or synergistic in combination compared with individual agents.","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},341277,1790722357,{"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},4398048950312,"https://ap-avatar.wpscdn.com/avatar/400002538284de19e3c?_k=1778320343897328908","DOI: 10. 1002/cam4 .7291  \nRESEAR CH ARTICLE  \nTargeting the core program of metastasis with a novel drug combination  \nGulimirerouzi Fnu | Georg F. Weber   \nJames L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA  \nCorrespondence  \nGeorg F. Weber, James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, 231 Albert Sabin Way, OH 45267-0514, USA.  \n[Email:](Email: georg.weber@uc.edu)[ georg.weber@uc.edu](Email: georg.weber@uc.edu)  \nFunding information  \nNational Center for Advancing Translational Sciences of the National Institutes of Health, Grant/Award Number: 2UL1TR001425; National Cancer Institute, Grant/Award Number: CA224104; Steven Goldman Memorial  \nAbstract  \nBackground: We previously reported that metastases are generally characterized by a core program of gene expression that activates tissue remodeling/ vascularization, alters ion homeostasis, induces the oxidative metabolism, and silences extracellular matrix interactions. This core program distinguishes metastases from their originating primary tumors as well as from their destination host tissues. Therefore, the gene products involved are potential targets for antimetastasis drug treatment.  \nMethods: Because the silencing of extracellular matrix interactions predisposes to anoiks in the absence of active survival mechanisms, we tested inhibitors against the other three components.  \nResults: Individually, the low-specificity VEGFR blocker pazopanib (in vivo combined with marimastat), the antioxidant dimethyl sulfoxide (or the substitute atovaquone, which is approved for internal administration), and the ionic modulators bumetanide and tetrathiomolybdate inhibited soft agar colony formation by breast and pancreatic cancer cell lines. The individual candidate agents have a record of use in humans (with limited efficacy when administered individually) and are available for repurposing. In combination, the effects of these drugs were additive or synergistic. In two mouse models of cancer (utilizing 4T1 cells or B16-F10 cells), the combination treatment with these medications, applied immediately (to prevent metastasis formation) or after a delay (to suppress established metastases), dramatically reduced the occurrence of disseminated foci. Conclusions: The combination of tissue remodeling inhibitors, suppressors of the oxidative metabolism, and ion homeostasis modulators has very strong promise for the treatment of metastases by multiple cancers.  \nKEYWORDS  \nextracellular matrix, gene expression, ion homeostasis, metabolism, metastasis, vascularization  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.  \n1 | INTRODUCTION  \nEven though the chemotherapy of primary tumors has been increasingly successful, the drug treatment of metastases has been compromised by low success rates. A likely reason lies in the clinical proclivity to treat the disseminated growths with the same agents that have been devised to counteract the primary tumors. Metastases, however, evolve their gene expression patterns to differentiate them from their originating tumors as well as from the implantation organ.1 There are site-specific changes,2 but they would be difficult to control with chemotherapy, because each site of dissemination would require a separate set of drugs. The core signature of metastases in general offers the possibility for intervention. Drug cocktails, which impact the phenotypic characteristics that are uniquely imparted by the gene expression programs of all metastases, may be most suitable to eradicate disseminated cancers.  \nSince the mid-1980s (with the discovery of individual genes that direct or suppress metastasis), it has become increasingly apparent that the","cbCaibOXAOs6ED37","https://ap.wps.com/l/cbCaibOXAOs6ED37","pdf",15029331,18,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What is the central idea behind targeting metastasis in this study?\",\"answer\":\"Metastases share a conserved core gene-expression program that controls tissue remodeling/vascularization, ion homeostasis, oxidative metabolism, and extracellular-matrix interaction silencing. Targeting the gene products underlying this program is proposed as an anti-metastasis strategy.\"},{\"question\":\"How were the drug candidates evaluated in the experiments?\",\"answer\":\"Inhibitors were tested against the three components other than extracellular-matrix interaction silencing. The study assessed effects on soft-agar colony formation in breast and pancreatic cancer cell lines and then evaluated combinations in two mouse models.\"},{\"question\":\"What were the key findings for drug combinations in vivo?\",\"answer\":\"Across two mouse models, combination treatment—given either immediately to prevent metastasis formation or after a delay to suppress established metastases—dramatically reduced the occurrence of disseminated foci. Effects were additive or synergistic in combination compared with individual agents.\"}]","Targeting the core program of metastasis with a novel drug combination | PDF",1790041294,45]