[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-detail-331099-en":59,"doc-seo-331099-105":81},{"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":5,"data":60},{"doc_id":61,"user_id":62,"nickname":63,"user_avatar":64,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":66,"doc_content":67,"file_id":68,"file_url":69,"file_type":70,"file_size":71,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":72,"language":73,"language_code":74,"site_id":75,"html_lang":74,"table_of_contents":76,"faqs":77,"seo_title":78,"seo_description":66,"update_tm":79,"read_time":80,"preview_page_count":4},331099,8796095461610,"Oliver","https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Pediatric Tumors as Disorders of Development - The Case for In Vitro Modeling Based on Human Stem Cells","Despite improvements in outcomes, pediatric cancer remains a leading cause of non-accidental death in children. Genetic analyses highlight germline predisposition alongside cancer-specific somatic driver mutations, and show that when the cancer cell-of-origin transformation occurs strongly shapes tumor identity and therapeutic response. Future therapies may benefit from disease models that reproduce genetic context, cell-of-origin, and developmental vulnerability windows. Human stem cells can integrate these features and support rapid genetic and pharmacological testing. This review explains stem-cell modeling of pediatric cancers and compares it with other model modalities.","Pediatric Tumors as Disorders of Development: The Case for In Vitro Modeling Based on Human Stem Cells  \nCullen D. Clairmont 1,2 􀀁, Joanna J. Gell 1,2,3,4, and Ching C. Lau 1,2,3,4  \nCancer Control Volume 31: 1–15  \n© The Author(s) 2024  \nArticle reuse guidelines:  \n[sagepub.com/journals-permissions](sagepub.com/journals-permissions)  \n[DOI: 10.1177/10732748241270564](DOI: 10.1177/10732748241270564)[ ](DOI: 10.1177/10732748241270564)[journals.sagepub.com/home/ccx](journals.sagepub.com/home/ccx)  \nAbstract  \nDespite improvements in patient outcomes, pediatric cancer remains a leading cause of non-accidental death in children. Recent genetic analysis of patients with pediatric cancers indicates an important role for both germline genetic predisposition and cancer-specific somatic driver mutations. Increasingly, evidence demonstrates that the developmental timepoint at which the cancer cell-of-origin transforms is critical to tumor identity and therapeutic response. Therefore, future therapeutic development would be bolstered by the use of disease models that faithfully recapitulate the genetic context, cell-of-origin, and developmental window of vulnerability in pediatric cancers. Human stem cells have the potential to incorporate all of these characteristics into a pediatric cancer model, while serving as a platform for rapid genetic and pharmacological testing. In this review, we describe how human stem cells have been used to model pediatric cancers and how these models compare to other pediatric cancer model modalities.  \nPlain Language Summary  \nToday, pediatric cancer is a leading cause of non-accidental death in children. In order to further improve outcomes, it is important for researchers and clinicians alike to recognize how pediatric cancers are distinct from adult cancers. Inherited risk of cancer may play a greater role in pediatric cancer risk, and subsequent tumor-specific acquired driver mutations initiate tumor formation. However, there is substantial interaction between inherited and acquired mutations, which supports consideration of both simultaneously. Recent advancements in biotechnology, have improved matching between early cells of development and pediatric cancer cells, although cell-of-origin for certain pediatric central nervous system tumors remain elusive. Increasingly, evidence, particularly in pediatric medulloblastoma, demonstrates that the developmental timepoint at which the cancer cell-of-origin transforms is critical to tumor identity and therapeutic response. Therefore, future therapeutic development would be bolstered by the use of disease models that faithfully recapitulate the genetic context, cell-of-origin, and developmental window of pediatric cancers. Human stem cells have the potential to incorporate all of these characteristics into a pediatric cancer model, while serving as a platform for rapid genetic and pharmacological testing. In this review, we describe how human stem cells have been used to model pediatric cancers, how human these models compare to other pediatric cancer model modalities, and how these models can be improved in the future.  \n1 University of Connecticut School of Medicine, Farmington, CT, USA  \n2The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA  \n3Connecticut Children’s Medical Center, Center for Cancer and Blood Disorders, Hartford, CT, USA 4Division of Pediatric Hematology-Oncology, Department of Pediatrics, UConn Health, Farmington, CT, USA  \nCorresponding Author:  \nChing C. Lau, The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. [Email:](Email: Ching.lau@jax.org)[ Ching.lau@jax.org](Email: Ching.lau@jax.org)  \nCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons  \nAttribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use,  \nreproduction","cbCaimtZXKVkMqDD","https://ap.wps.com/l/cbCaimtZXKVkMqDD","pdf",949689,15,"English","en",105,"# Abstract\n# Plain Language Summary\n# Introduction\n# Keywords","[{\"question\":\"Why is developmental timing important for pediatric tumor biology and treatment response?\",\"answer\":\"Evidence indicates that the developmental timepoint when the cancer cell-of-origin transforms is critical for tumor identity and therapeutic response. Models that mirror this timing are therefore expected to improve therapy development.\"},{\"question\":\"What genetic factors contribute to pediatric cancer according to recent analyses?\",\"answer\":\"Recent genetic analyses point to an important role for both germline genetic predisposition and cancer-specific somatic driver mutations. The interaction between inherited and acquired mutations supports considering both simultaneously.\"},{\"question\":\"How do human stem cells contribute to pediatric cancer disease modeling?\",\"answer\":\"Human stem cells can incorporate the genetic context, the relevant cell-of-origin, and the developmental window of vulnerability into a single pediatric cancer model. They also provide a platform for rapid genetic and pharmacological testing, and the review compares these models with other modalities.\"}]","Pediatric Tumors as Disorders of Development - The Case for In Vitro Modeling Based on Human Stem Cells | PDF",1789991796,38,{"code":4,"msg":82,"data":83},"ok",{"site_id":75,"language":74,"slug":84,"title":65,"keywords":85,"description":66,"schema_data":86,"social_meta":140,"head_meta":142,"extra_data":144,"updated_unix":145},"pediatric-tumors-as-disorders-of-development-the-case-for-in-vitro-modeling-based-on-human-stem-cells","",{"@graph":87,"@context":139},[88,102,122],{"@type":89,"itemListElement":90},"BreadcrumbList",[91,95,97,100],{"item":92,"name":93,"@type":94,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":96,"name":9,"@type":94,"position":14},"https://docshare.wps.com/document/",{"item":98,"name":40,"@type":94,"position":99},"https://docshare.wps.com/document/research-report/",3,{"item":101,"name":65,"@type":94,"position":19},"https://docshare.wps.com/document/pediatric-tumors-as-disorders-of-development-the-case-for-in-vitro-modeling-based-on-human-stem-cells/331099/",{"url":101,"name":65,"@type":103,"image":104,"author":109,"headline":65,"publisher":111,"fileFormat":114,"inLanguage":74,"description":66,"dateModified":115,"datePublished":116,"encodingFormat":114,"isAccessibleForFree":117,"interactionStatistic":118},"DigitalDocument",{"url":105,"@type":106,"width":107,"height":108},"https://docshare.wps.com/thumbnails/pediatric-tumors-as-disorders-of-development-the-case-for-in-vitro-modeling-based-on-human-stem-cells/331099.png","ImageObject",300,407,{"name":63,"@type":110},"Person",{"url":92,"name":112,"@type":113},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":119,"interactionType":120,"userInteractionCount":34},"InteractionCounter",{"@type":121},"ViewAction",{"@type":123,"mainEntity":124},"FAQPage",[125,131,135],{"name":126,"@type":127,"acceptedAnswer":128},"Why is developmental timing important for pediatric tumor biology and treatment response?","Question",{"text":129,"@type":130},"Evidence indicates that the developmental timepoint when the cancer cell-of-origin transforms is critical for tumor identity and therapeutic response. Models that mirror this timing are therefore expected to improve therapy development.","Answer",{"name":132,"@type":127,"acceptedAnswer":133},"What genetic factors contribute to pediatric cancer according to recent analyses?",{"text":134,"@type":130},"Recent genetic analyses point to an important role for both germline genetic predisposition and cancer-specific somatic driver mutations. The interaction between inherited and acquired mutations supports considering both simultaneously.",{"name":136,"@type":127,"acceptedAnswer":137},"How do human stem cells contribute to pediatric cancer disease modeling?",{"text":138,"@type":130},"Human stem cells can incorporate the genetic context, the relevant cell-of-origin, and the developmental window of vulnerability into a single pediatric cancer model. They also provide a platform for rapid genetic and pharmacological testing, and the review compares these models with other modalities.","https://schema.org",{"og:url":101,"og:type":141,"og:title":65,"og:site_name":112,"og:description":66},"article",{"robots":143,"canonical":101},"index,follow",{"doc_id":61,"site_id":75},1790055831]