[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-336928-105":59,"doc-detail-336928-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","systemic-treatments-for-radioiodine-refractory-thyroid-cancers-review","Systemic treatments for radioiodine-refractory thyroid cancers - review","","Systemic treatments for radioiodine-refractory thyroid cancers (RAI-RTCs) are reviewed with emphasis on how reduced radioiodine uptake undermines standard care for differentiated thyroid cancers. The review links RAI-refractoriness to genetic mutations and rearrangements that disrupt signaling pathways such as MAPK and PI3K, causing thyroid dedifferentiation and impaired sodium/iodide symporter function. It summarizes current systemic options, including multikinase inhibitors as first- and second-line therapy, and discusses ongoing trials for selective kinase inhibitors, immune checkpoint inhibitors, and combinations.",{"@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/systemic-treatments-for-radioiodine-refractory-thyroid-cancers-review/336928/",{"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/systemic-treatments-for-radioiodine-refractory-thyroid-cancers-review/336928.png","ImageObject",300,407,{"name":92,"@type":93},"Skyler","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What makes radioiodine-refractory thyroid cancers different from other differentiated thyroid cancers?","Question",{"text":112,"@type":113},"RAI-RTCs have decreased radioiodine uptake, so standard surgery with or without radioiodine and levothyroxine inhibition often fails to deliver lasting control after treatment progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which molecular pathways are described as contributing to RAI refractoriness?",{"text":117,"@type":113},"Genetic mutations and rearrangements affecting RTKs, RAS, BRAF, and TERTp are described as activating signaling pathways such as MAPK and PI3K, leading to thyroid dedifferentiation and sodium/iodide symporter dysfunction.",{"name":119,"@type":110,"acceptedAnswer":120},"What systemic treatments are highlighted as current and emerging options?",{"text":121,"@type":113},"The review highlights multikinase inhibitors such as lenvatinib and sorafenib for first-line therapy and cabozantinib for second-line therapy. It also describes ongoing clinical trials evaluating selective kinase inhibitors, immune checkpoint inhibitors, and combination approaches, including strategies that may restore RAI uptake.","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},336928,1790207470,{"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":44,"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},2336464648746,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","TYPE Review  \nPUBLISHED 15 October 2024  \nDOI 10.3389/fendo.2024.1346476  \nOPEN ACCESS  \nEDITED BY  \nMaria João Bugalho,  \nSanta Maria Hospital, Portugal  \nREVIEWED BY  \nErika Abelleira,  \nHospital de Clnicas Jose´ de San Martn, Argentina  \nChae Moon Hong, Kyungpook National University, Republic of Korea  \n*CORRESPONDENCE  \nHuiwen Tan  \n [huiwent2016@scu.edu.cn](huiwent2016@scu.edu.cn)[ ](huiwent2016@scu.edu.cn)Jianwei Li  \n[jerryli678@hotmail.com](jerryli678@hotmail.com)  \n†These authors have contributed equally to this work and share first authorship  \nRECEIVED 20 February 2024  \nACCEPTED 27 September 2024  \nPUBLISHED 15 October 2024  \nCITATION  \nChen P, Yao Y, Tan H and Li J (2024)  \nSystemic treatments for radioiodinerefractory thyroid cancers.  \nFront. Endocrinol. 15:1346476 .  \ndoi: 10.3389/fendo.2024.1346476  \nCOPYRIGHT  \n© 2024 Chen, Yao, Tan and Li. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nSystemic treatments for radioiodine-refractory thyroid cancers  \nPiaohong Chen †, Yu Yao †, Huiwen Tan* and Jianwei Li*  \nDivision of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China  \nDifferentiated thyroid cancers (DTCs) constitute the primary histological subtype within thyroid cancer . Due to DTCs ’ distinctive radioiodine (RAI) uptake mechanism, standard treatment involving surgery, with or without adjunctive therapy using RAI and levothyroxine inhibition, typically yields favorable prognoses for the majority of patients with DTCs. However, this favorable outcome does not extend to individuals with decreased RAI uptake, termed radioiodine-refractory thyroid cancers (RAI-RTCs) . Recent research has revealed that the genetic mutations and gene rearrangements affecting sites such as RTKs, RAS, BRAF and TERTp lead to structural and functional abnormalities in encoded proteins. These abnormalities aberrantly activate signaling pathways like the mitogen-activated protein kinase (MAPK) and phos phatidylinositol-3-hydroxykinase (PI3K) signaling pathways, resulting in thyroid cells dedifferentiation, sodium/iodide symporter (NIS) dysfunction, and consequent the RAI-refractory nature of DTCs. Targeted therapy tailored to mutations presents a promising avenue for the treatment of RAI-RTCs. Lenvatinib and sorafenib, multi-kinase inhibitors, represent the standard first-line systemic treatment options, while cabozantinib is the standard second-line treatment option, for this purpose. Furthermore, ongoing clinical trials are exploring selective kinase inhibitors, immune checkpoint inhibitors, and combination therapies. Notably, numerous clinical trials have demonstrated that selective kinase inhibitors like BRAF, MEK and mTOR inhibitors can restore RAI uptake in tumor cells. However, further validation through multicenter, large-sample, double-blinded randomized controlled trials are essential. Enhanced treatment strategies and innovative therapies are expected to benefit a broader spectrum of patients as these advancements progress.  \nKEYWORDS  \nradioiodine-refractory thyroid cancers, sodium/iodide symporter, mitogen-activated protein kinase, phosphatidylinositol-3-hydroxykinase, TERTp, tyrosine kinase inhibitors, systemic treatments  \nFrontiers in Endocrinology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nThyroid cancer is the most prevalent malignancy within endocrine system (1) . According to data from GLOBOCAN 2020 by the International Agency for Research on Cancer, the year 2020 witnessed around 586,000 new cases of thyroid cancer globally, ranking it ninth among all cancers (2) . The t","cbCaippq484omtTd","https://ap.wps.com/l/cbCaippq484omtTd","pdf",1299321,15,"English","# 1 Introduction\n# 2 Review\n## 2.1 Definition of RAI-RTCs","[{\"question\":\"What makes radioiodine-refractory thyroid cancers different from other differentiated thyroid cancers?\",\"answer\":\"RAI-RTCs have decreased radioiodine uptake, so standard surgery with or without radioiodine and levothyroxine inhibition often fails to deliver lasting control after treatment progression.\"},{\"question\":\"Which molecular pathways are described as contributing to RAI refractoriness?\",\"answer\":\"Genetic mutations and rearrangements affecting RTKs, RAS, BRAF, and TERTp are described as activating signaling pathways such as MAPK and PI3K, leading to thyroid dedifferentiation and sodium/iodide symporter dysfunction.\"},{\"question\":\"What systemic treatments are highlighted as current and emerging options?\",\"answer\":\"The review highlights multikinase inhibitors such as lenvatinib and sorafenib for first-line therapy and cabozantinib for second-line therapy. It also describes ongoing clinical trials evaluating selective kinase inhibitors, immune checkpoint inhibitors, and combination approaches, including strategies that may restore RAI uptake.\"}]","Systemic treatments for radioiodine-refractory thyroid cancers - review | PDF",1790017101,38]