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Targeted therapies have expanded, including FDA-approved antiangiogenic multikinase inhibitors and more recent RET- and NTRK-specific kinase inhibitors, along with BRAF+MEK options for BRAF-mutated disease. Because current treatments are rarely curative and progression is common, research emphasizes mechanisms of resistance to tyrosine kinase inhibitors and strategies to overcome them, including immunotherapy, redifferentiation, and second-generation kinase inhibitors.",{"@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/review-article-new-treatments-for-advanced-differentiated-thyroid-cancers-and-potential-mechanisms-of-drug-resistance-review/405861/",{"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/review-article-new-treatments-for-advanced-differentiated-thyroid-cancers-and-potential-mechanisms-of-drug-resistance-review/405861.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",16,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What progress has been made in treating advanced RR-DTCs?","Question",{"text":113,"@type":114},"Molecular characterization and next-generation sequencing have enabled FDA-approved targeted therapies, including multikinase inhibitors and RET/NTRK inhibitors, with BRAF+MEK therapy also used for BRAF-mutated disease.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why is identifying drug resistance mechanisms important?",{"text":118,"@type":114},"Most available treatments are not curative and many patients eventually progress, so research focuses on resistance to tyrosine kinase inhibitors and approaches to overcome it.",{"name":120,"@type":111,"acceptedAnswer":121},"How is radioiodine-refractory differentiated thyroid cancer defined clinically?",{"text":122,"@type":114},"RAI-refractory disease is defined using criteria such as absent uptake outside the thyroid bed, loss of RAI concentration in previously RAI-avid tumors, heterogeneous uptake, and progression despite adequate RAI exposure over an expected time frame.","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},405861,1790765226,{"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":146,"preview_page_count":4},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","TYPE Review  \nPUBLISHED 26 June 2023  \nDOI 10.3389/fendo.2023.1176731  \nOPEN ACCESS  \nEDITED BY  \nJoana Simões-Pereira,  \nInstituto Portuguˆes de Oncologia de Lisboa Francisco Gentil, Portugal  \nREVIEWED BY Alessandro Prete, University of Pisa, Italy Christine Spitzweg,  \nLMU Munich University Hospital, Germany  \n*CORRESPONDENCE Ramona Dadu  \n [rdadu@mdanderson.org](rdadu@mdanderson.org)  \nRECEIVED 28 February 2023  \nACCEPTED 05 June 2023  \nPUBLISHED 26 June 2023  \nCITATION  \nHamidi S, Hofmann M-C, Iyer PC, Cabanillas ME, Hu MI, Busaidy NL and Dadu R (2023) Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance.  \nFront. Endocrinol. 14:1176731 .  \ndoi: 10.3389/fendo.2023.1176731  \nCOPYRIGHT  \n© 2023 Hamidi, Hofmann, Iyer, Cabanillas, Hu, Busaidy and Dadu. 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.  \nReview article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance  \nSarah Hamidi, Marie-Claude Hofmann, Priyanka C. Iyer, Maria E. Cabanillas, Mimi I. Hu, Naifa L. Busaidy and Ramona Dadu*  \nDepartment of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, United States  \nThe treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RRDTCs, including antiangiogenic multikinase inhibitors, and more recently, fusionspecific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in many centers. However, none of the currently available treatments are curative, and most patients will ultimately show progression. Current research efforts are therefore focused on identifying resistance mechanisms to tyrosine kinase inhibitors and ways to overcome them. Various novel treatment strategies are under investigation, including immunotherapy, redifferentiation therapy, and second-generation kinase inhibitors. In this review, we will discuss currently available drugs for advanced RR-DTCs, potential mechanisms of drug resistance and future therapeutic avenues.  \nKEYWORDS  \ndrug resistance, immunotherapy, neoadjuvant, metastatic thyroid cancer, radioiodine refractoriness, tyrosine kinase inhibitor, novel treatments  \nIntroduction  \nDifferentiated thyroid cancers (DTCs) have an excellent prognosis in most patients, with an overall 5-year relative survival rate of 98.4% according to the SEER database (1) . However, a subtype of patients, representing 5-10% of all DTCs, will develop distant metastasis, most frequently in the lungs and bones (2). Prognosis remains favorable as long  \nFrontiers in Endocrinology 01 [frontiersin.org](frontiersin.org)  \nas metastatic disease is radioiodine-avid (3) . Yet, 50% of metastatic DTCs are refractory to radioactive iodine (RAI), which is associated with poor outcomes and a 10-year survival rate of about 10%(4) . On the other hand, many patients with advanced radioiodine refractory DTC (RR-DTC) can have an indolent or slowly progressive disease for many years. Thus, as multiple advances have been made in the treatment of advanced RR-DTCs in the last decade","cbCaidPRcXTT9rLK","https://ap.wps.com/l/cbCaidPRcXTT9rLK","pdf",2565029,18,"English","# Introduction\n## When to treat RR-DTC","[{\"question\":\"What progress has been made in treating advanced RR-DTCs?\",\"answer\":\"Molecular characterization and next-generation sequencing have enabled FDA-approved targeted therapies, including multikinase inhibitors and RET/NTRK inhibitors, with BRAF+MEK therapy also used for BRAF-mutated disease.\"},{\"question\":\"Why is identifying drug resistance mechanisms important?\",\"answer\":\"Most available treatments are not curative and many patients eventually progress, so research focuses on resistance to tyrosine kinase inhibitors and approaches to overcome it.\"},{\"question\":\"How is radioiodine-refractory differentiated thyroid cancer defined clinically?\",\"answer\":\"RAI-refractory disease is defined using criteria such as absent uptake outside the thyroid bed, loss of RAI concentration in previously RAI-avid tumors, heterogeneous uptake, and progression despite adequate RAI exposure over an expected time frame.\"}]","Review article: new treatments for advanced differentiated thyroid cancers and potential mechanisms of drug resistance - Review | PDF",1790562183,45]