[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-360228-105":59,"doc-detail-360228-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","combinational-studies-of-bold-100kp1339-with-established-chemotherapeutics-in-gastrointestinal-multicellular-tumor-spheroids","Combinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids","","BOLD-100 (KP1339), a ruthenium(III) prodrug under clinical investigation as a co-therapeutic anticancer agent, is evaluated for in vitro combination effects with oxaliplatin, 5-FU, cisplatin, or SN38 in multicellular tumor spheroids. The study focuses on its non-DNA target, GRP78, a mediator of the unfolded protein response. Gastric and colorectal cancer spheroid models were assessed for cytotoxicity, synergism/antagonism, reactive oxygen species generation, and apoptosis or necrosis. Results show distinct chemosensitivities by spheroid origin and partially synergistic combination effects, with consistent ROS increases for oxaliplatin-based combinations and no antagonism signals.",{"@graph":69,"@context":123},[70,84,106],{"@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/combinational-studies-of-bold-100kp1339-with-established-chemotherapeutics-in-gastrointestinal-multicellular-tumor-spheroids/360228/",{"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/combinational-studies-of-bold-100kp1339-with-established-chemotherapeutics-in-gastrointestinal-multicellular-tumor-spheroids/360228.png","ImageObject",300,407,{"name":92,"@type":93},"Cipher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is BOLD-100 (KP1339) and why was it tested in combinations?","Question",{"text":113,"@type":114},"BOLD-100 is a ruthenium(III) prodrug investigated as a co-therapeutic anticancer drug. It targets GRP78 and may trigger ER stress and cell death, making it a candidate for combination therapy with established chemotherapeutics.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which drugs were combined with BOLD-100, and in what tumor models?",{"text":118,"@type":114},"BOLD-100 was combined with oxaliplatin, 5-FU, cisplatin, or SN38. Experiments used gastric (MKN45, NCI-N87) and colorectal (HCT116, HT29) cancer cell lines grown as multicellular tumor spheroids.",{"name":120,"@type":111,"acceptedAnswer":121},"How were therapeutic effects and interactions measured in the study?",{"text":122,"@type":114},"The study measured cytotoxic activity and assessed synergism or antagonism using Chou and Talalay’s algorithm. It also evaluated reactive oxygen species formation and induction of apoptosis and necrosis in spheroid models.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},360228,1790176945,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":36},687208528416,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Cancer Chemotherapy and Pharmacology (2026) 96:57  \n[https://doi.org/10.1007/s00280-026-04902-z](https://doi.org/10.1007/s00280-026-04902-z)  \nORIGINAL ARTICLE  \nCombinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids  \nDominik Wenisch1 · Slavica Ždravac1 · Michael A. Jakupec1,2 · Franz Jirsa3 · Bernhard K. Keppler1,2  \nReceived: 18 December 2025 / Accepted: 3 May 2026 © The Author(s) 2026  \nAbstract  \nBOLD-100, a ruthenium(III) prodrug also known as KP1339, is currently under clinical investigation for its suitability as a co-therapeutic anticancer drug. Unlike platinum-based chemotherapeutics, it has unique non-DNA targets, mainly GRP78, an enzyme responsible for signaling related to protein folding in the ER. Inhibition of this key mediator of the “unfolded protein response” may lead to cell death eventually. The purpose of this study was to assess in vitro the impact of BOLD-100 combinations with oxaliplatin, 5-FU, cisplatin or SN38 in multicellular tumor spheroids (MCTSs) compared to single-drug treatments. Gastric (MKN45, NCI-N87) and colorectal cancer (HCT116, HT29) cell lines were chosen, corresponding to the clinical trial in which patients with tumors of these origins are being treated. Biological effects investigated in this study include cytotoxic activity, synergism/antagonism based on Chou and Talalay’s algorithm, formation of reactive oxygen species (ROS) and induction of apoptosis and necrosis. Cytotoxicity tests showed vastly different chemosensitivities in MCTSs of the same tumor origin. In both tumor entities, partially synergistic effects were revealed when BOLD-100 was combined with the drugs mentioned above. The DCFH-DA assay suggested consistent increases of ROS levels after treatment with oxaliplatin and, with restrictions, its combination with BOLD-100 . Apoptosis and necrosis were induced in the spheroid models by single-drug and combined treatment, with no hints at antagonism in the combination settings. In conclusion, these findings emphasize the potential of BOLD-100 for combination therapy of gastric and colorectal cancers.  \nKeywords Colon cancer · Combination therapy · Gastric cancer · Multicellular tumor spheroids · Ruthenium drug · In vitro studies  \nIntroduction  \nChemotherapy is a powerful treatment modality for therapy of various solid tumor entities. Platinum-based drugs, such as cisplatin, oxaliplatin and carboplatin, are still among the most frequently applied cancer chemotherapeutics [1] .  \n􀀍 Michael A. Jakupec [michael.jakupec@univie.ac.at](michael.jakupec@univie.ac.at)  \n1 Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Strasse 42, 1090 Vienna, Austria  \n2 Research Cluster “Translational Cancer Therapy Research”, University of Vienna, Währinger Strasse 42, 1090 Vienna, Austria  \n3 Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria  \nBeside their property of attacking cancer cells, adverse effects, such as neurotoxicity, nephrotoxicity or myelosuppression [2], occur frequently due to unspecific interactions with normal cells, thereby limiting patients’ tolerance to these therapeutic approaches.  \nA well-established alternative to single drugs is their combined application. Enhancement of therapeutic impact of a potent drug with simultaneous diminution of adverse effects by one or more auxiliary drug(s) might be an optimal combinational strategy [3–5] . Beside platinum-based chemotherapeutics, various ruthenium (Ru) complexes have shown anticancer activity in vitro and in vivo, and a few even have proceeded to the stage of clinical evaluation [6– 8] . BOLD-100, a Ru(III) pro-drug also known as KP1339, is currently investigated in patients with advanced gastrointestinal tumors in a clinical phase II trial (NCT04421820)  \n[9] . Over the course of the trial, this Ru-based drug already showed promising benefici","cbCail1joTYlaOC6","https://ap.wps.com/l/cbCail1joTYlaOC6","pdf",2090862,16,"English","# Abstract\n# Introduction","[{\"question\":\"What is BOLD-100 (KP1339) and why was it tested in combinations?\",\"answer\":\"BOLD-100 is a ruthenium(III) prodrug investigated as a co-therapeutic anticancer drug. It targets GRP78 and may trigger ER stress and cell death, making it a candidate for combination therapy with established chemotherapeutics.\"},{\"question\":\"Which drugs were combined with BOLD-100, and in what tumor models?\",\"answer\":\"BOLD-100 was combined with oxaliplatin, 5-FU, cisplatin, or SN38. Experiments used gastric (MKN45, NCI-N87) and colorectal (HCT116, HT29) cancer cell lines grown as multicellular tumor spheroids.\"},{\"question\":\"How were therapeutic effects and interactions measured in the study?\",\"answer\":\"The study measured cytotoxic activity and assessed synergism or antagonism using Chou and Talalay’s algorithm. It also evaluated reactive oxygen species formation and induction of apoptosis and necrosis in spheroid models.\"}]","Combinational studies of BOLD-100/KP1339 with established chemotherapeutics in gastrointestinal multicellular tumor spheroids | PDF",1790139108]