[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332988-105":3,"doc-detail-332988-en":81,"detail-sidebar-cat-0-en-105":98},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","metabolic-profiling-of-patient-derived-organoids-reveals-nucleotide-synthesis-as-a-metabolic-vulnerability-in-malignant-rhabdoid-tumors","Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors","","Malignant rhabdoid tumor (MRT) is a highly aggressive childhood cancer with limited effective options. Using patient-derived tumor organoids (tumoroids), the study maps metabolic landscapes across pediatric cancers and identifies nucleotide biosynthesis as a specific metabolic vulnerability in MRT. Gene expression and mass-spectrometry metabolite profiling show strong activation of de novo nucleotide synthesis in MRT. In vitro treatment of MRT tumoroids with methotrexate (MTX) and BAY-2402234 reduces nucleotide levels and triggers apoptosis, and MTX also demonstrates growth-reducing efficacy in vivo in patient-derived xenograft models.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/metabolic-profiling-of-patient-derived-organoids-reveals-nucleotide-synthesis-as-a-metabolic-vulnerability-in-malignant-rhabdoid-tumors/332988/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/metabolic-profiling-of-patient-derived-organoids-reveals-nucleotide-synthesis-as-a-metabolic-vulnerability-in-malignant-rhabdoid-tumors/332988.png","ImageObject",300,407,{"name":42,"@type":43},"Valentina","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-11","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What metabolic process is identified as a vulnerability in malignant rhabdoid tumors (MRT)?","Question",{"text":63,"@type":64},"The study identifies de novo nucleotide biosynthesis as a metabolic vulnerability specific to MRT. Inhibiting nucleotide synthesis reduces nucleotide levels and induces apoptosis in MRT tumoroids.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do methotrexate (MTX) and BAY-2402234 affect MRT tumoroids?",{"text":68,"@type":64},"Treatment with MTX and BAY-2402234 lowers nucleotide levels in MRT tumoroids and induces apoptosis in vitro. MTX also reduces MRT growth in vivo.",{"name":70,"@type":61,"acceptedAnswer":71},"What models and methods are used to study MRT metabolism?",{"text":72,"@type":64},"Patient-derived tumor organoids (tumoroids) are used to map metabolic landscapes, combining gene expression analyses with metabolite profiling by mass spectrometry. In vivo efficacy is tested using MRT patient-derived xenograft mouse models.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332988,1790196737,{"code":4,"msg":82,"data":83},"success",{"doc_id":79,"user_id":84,"nickname":42,"user_avatar":85,"doc_module":4,"category_id":55,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":86,"file_id":87,"file_url":88,"file_type":89,"file_size":90,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":91,"language":92,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":93,"faqs":94,"seo_title":95,"seo_description":12,"update_tm":96,"read_time":97,"preview_page_count":4},13056703020460,"https://ap-avatar.wpscdn.com/avatar/be000253dac470eee5d?_k=1778207105932848923","Article  \nMetabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors  \nGraphical abstract  \nHighlights  \nAuthors  \nMarjolein M.G. Kes,  \nFrancisco Morales-Rodriguez, Esther A. Zaal, ..., Jeroen W.A. Jansen, Celia R. Berkers, Jarno Drost  \nCorrespondence  \n[c.r.berkers@uu.nl](c.r.berkers@uu.nl) (C.R.B.),  \n[j.drost@prinsesmaximacentrum.nl](j.drost@prinsesmaximacentrum.nl) (J.D.)  \nIn brief  \nMalignant rhabdoid tumor (MRT) is an aggressive childhood cancer with limited treatment options. Using patient-derived tumor organoids (tumoroids), Kes et al. identify nucleotide biosynthesis as a vulnerability in MRT. Treatment with methotrexate (MTX) and BAY-2402234 reduced nucleotide levels and induced apoptosis in vitro, with MTX demonstrating reduced MRT growth in vivo.  \nd Metabolic fingerprints of pediatric kidney tumors are preserved in tumoroids  \nd De novo nucleotide synthesis is highly activated in MRT and AT/RT  \nd Nucleotide synthesis inhibition is specifically cytotoxic in MRT and AT/RT  \nd Nucleotide synthesis inhibition delays MRT growth in vivo  \nKes et al., 2025, Cell Reports Medicine 6, 101878  \nJanuary 21, 2025 ª 2024 The Author(s) . Published by Elsevier Inc.  \n[https://doi.org/10.1016/j.xcrm.2024.101878](https://doi.org/10.1016/j.xcrm.2024.101878)  \nll  \nll  \nOPEN ACCESS  \nArticle  \nMetabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors  \nMarjolein M.G. Kes,1,2,3,6 Francisco Morales-Rodriguez,1,2,6 Esther A. Zaal,3,6 Terezinha de Souza,1,2 Natalie Proost,4 Marieke van de Ven,4 Marry M. van den Heuvel-Eibrink,1,5 Jeroen W.A. Jansen,3 Celia R. Berkers,3,* and Jarno Drost1,2,7,*  \n1Princess M´axima Center for Pediatric Oncology, Utrecht, the Netherlands  \n2Oncode Institute, Utrecht, the Netherlands  \n3Division Cell Biology, Metabolism & Cancer, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands  \n4Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing (MCCA), Netherlands Cancer Institute, Amsterdam, the Netherlands  \n5Division of Child Health, Wilhelmina Children’s Hospital, Utrecht University, Utrecht, the Netherlands  \n6These authors contributed equally  \n7Lead contact  \n*Correspondence: [c.r.berkers@uu.nl](c.r.berkers@uu.nl) (C. R. B.), [j.drost@prinsesmaximacentrum.nl](j.drost@prinsesmaximacentrum.nl) (J. D.) [https://doi.org/10.1016/j.xcrm.2024.101878](https://doi.org/10.1016/j.xcrm.2024.101878)  \nSUMMARY  \nMalignant rhabdoid tumor (MRT) is one of the most aggressive childhood cancers for which no effective treatment options are available. Reprogramming of cellular metabolism is an important hallmark of cancer, with various metabolism-based drugs being approved as a cancer treatment. In this study, we use patient-derived tumor organoids (tumoroids) to map the metabolic landscape of several pediatric cancers. Combining gene expression analyses and metabolite profiling using mass spectrometry, we find nucleotide biosynthesis to bea particular vulnerability of MRT. Treatment of MRT tumoroids with de novo nucleotide synthesis inhibitors methotrexate (MTX) and BAY-2402234 lowers nucleotide levels in MRT tumoroids and induces apoptosis. Lastly, we demonstrate in vivo efficacy of MTX in MRT patient-derived xenograft (PDX) mouse models. Our study reveals nucleotide biosynthesis as an MRT-specific metabolic vulnerability, which can ultimately lead to better treatment options for children suffering from this lethal pediatric malignancy.  \nINTRODUCTION  \nKidney cancer is the second most common solid cancer in children. Pediatric kidney tumors mostly encompass Wilms tumors, representing 􀀁 80% of cases, but also renal cell carcinomas (RCCs), clear cell sarcomas, and malignant rhabdoid tumors (extracranial MRT [ecMRT]) can occur.1 Malignant rhabdoid tumors (MRTs) are particularly aggressive malignanci","cbCaihVMU6Vxd0ed","https://ap.wps.com/l/cbCaihVMU6Vxd0ed","pdf",4453232,19,"English","# Summary\n# Highlights\n# Introduction\n## Pediatric kidney tumors and MRT/AT/RT background\n## Metabolic rewiring and rationale for metabolic inhibitors","[{\"question\":\"What metabolic process is identified as a vulnerability in malignant rhabdoid tumors (MRT)?\",\"answer\":\"The study identifies de novo nucleotide biosynthesis as a metabolic vulnerability specific to MRT. Inhibiting nucleotide synthesis reduces nucleotide levels and induces apoptosis in MRT tumoroids.\"},{\"question\":\"How do methotrexate (MTX) and BAY-2402234 affect MRT tumoroids?\",\"answer\":\"Treatment with MTX and BAY-2402234 lowers nucleotide levels in MRT tumoroids and induces apoptosis in vitro. MTX also reduces MRT growth in vivo.\"},{\"question\":\"What models and methods are used to study MRT metabolism?\",\"answer\":\"Patient-derived tumor organoids (tumoroids) are used to map metabolic landscapes, combining gene expression analyses with metabolite profiling by mass spectrometry. In vivo efficacy is tested using MRT patient-derived xenograft mouse models.\"}]","Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors | PDF",1790000298,48,{"code":4,"msg":82,"data":99},[100,104,108,112,117,122,127,130,135,138,142],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":101,"show_sort_weight":102,"slug":103},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":105,"show_sort_weight":106,"slug":107},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":109,"show_sort_weight":110,"slug":111},"Exam",70,"exam",{"id":113,"doc_module":4,"doc_module_name":25,"category_name":114,"show_sort_weight":115,"slug":116},5,"Comic",60,"comic",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":119,"show_sort_weight":120,"slug":121},6,"Technology",50,"technology",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":125,"slug":126},7,"Healthcare",40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":128,"slug":129},30,"research-report",{"id":131,"doc_module":4,"doc_module_name":25,"category_name":132,"show_sort_weight":133,"slug":134},9,"Religion & Spirituality",20,"religion-spirituality",{"id":133,"doc_module":4,"doc_module_name":25,"category_name":136,"show_sort_weight":133,"slug":137},"World Cup","world-cup",{"id":139,"doc_module":4,"doc_module_name":25,"category_name":140,"show_sort_weight":139,"slug":141},10,"Lifestyle","lifestyle",{"id":91,"doc_module":4,"doc_module_name":25,"category_name":143,"show_sort_weight":113,"slug":144},"General","general"]