{"id":"https://openalex.org/W7225802902","doi":"https://doi.org/10.3389/fendo.2026.2017741","title":"Determinants of redifferentiation response in radioiodine-refractory differentiated thyroid cancer: from lineage reversibility to therapeutic radioiodine delivery","display_name":"Determinants of redifferentiation response in radioiodine-refractory differentiated thyroid cancer: from lineage reversibility to therapeutic radioiodine delivery","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225802902","doi":"https://doi.org/10.3389/fendo.2026.2017741"},"language":"en","primary_location":{"id":"doi:10.3389/fendo.2026.2017741","doi":"https://doi.org/10.3389/fendo.2026.2017741","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fendo.2026.2017741","pdf_url":null,"source":{"id":"https://openalex.org/S2597401208","display_name":"Frontiers in Endocrinology","issn_l":"1664-2392","issn":["1664-2392"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","ki-jl-1","medline","norway-1","oarl","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Endocrinology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3389/fendo.2026.2017741","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5100353584","display_name":"Hao Chen","orcid":"https://orcid.org/0000-0002-7509-5820","observed_orcids":["https://orcid.org/0000-0002-7509-5820"]},"institutions":[{"id":"https://openalex.org/I4210113195","display_name":"Gannan Medical University","ror":"https://ror.org/01tjgw469","country_code":"CN","type":"education","lineage":["https://openalex.org/I4210113195"]},{"id":"https://openalex.org/I4210133784","display_name":"First Affiliated Hospital of Gannan Medical University","ror":"https://ror.org/040gnq226","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210133784"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Hao Chen","raw_affiliation_strings":["Department of Clinical Medicine, First Clinical College, Gannan Medical University","Longnan Hospital, First Affiliated Hospital of Gannan Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Clinical Medicine, First Clinical College, Gannan Medical University","institution_ids":["https://openalex.org/I4210113195"]},{"raw_affiliation_string":"Longnan Hospital, First Affiliated Hospital of Gannan Medical University","institution_ids":["https://openalex.org/I4210133784"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055879485","display_name":"Xiaoqing Chen","orcid":"https://orcid.org/0000-0002-4133-9751","observed_orcids":["https://orcid.org/0000-0002-4133-9751"]},"institutions":[{"id":"https://openalex.org/I4210113195","display_name":"Gannan Medical University","ror":"https://ror.org/01tjgw469","country_code":"CN","type":"education","lineage":["https://openalex.org/I4210113195"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xiaoqing Chen","raw_affiliation_strings":["Department of Clinical Medicine, First Clinical College, Gannan Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Clinical Medicine, First Clinical College, Gannan Medical University","institution_ids":["https://openalex.org/I4210113195"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5153417741","display_name":"Jiajun Tang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210113195","display_name":"Gannan Medical University","ror":"https://ror.org/01tjgw469","country_code":"CN","type":"education","lineage":["https://openalex.org/I4210113195"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jiajun Tang","raw_affiliation_strings":["Department of Clinical Medicine, First Clinical College, Gannan Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Clinical Medicine, First Clinical College, Gannan Medical University","institution_ids":["https://openalex.org/I4210113195"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102892316","display_name":"Yang Xie","orcid":"https://orcid.org/0000-0003-1368-4264","observed_orcids":["https://orcid.org/0000-0003-1368-4264","https://orcid.org/0009-0009-9882-9477"]},"institutions":[{"id":"https://openalex.org/I4210133784","display_name":"First Affiliated Hospital of Gannan Medical University","ror":"https://ror.org/040gnq226","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210133784"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yang Xie","raw_affiliation_strings":["Department of Thyroid and Hernia Surgery, First Affiliated Hospital of Gannan Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Thyroid and Hernia Surgery, First Affiliated Hospital of Gannan Medical University","institution_ids":["https://openalex.org/I4210133784"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5161480858","display_name":"Xiangtai Zeng","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210133784","display_name":"First Affiliated Hospital of Gannan Medical University","ror":"https://ror.org/040gnq226","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210133784"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Xiangtai Zeng","raw_affiliation_strings":["Department of Thyroid and Hernia Surgery, First Affiliated Hospital of Gannan Medical University","Longnan Hospital, First Affiliated Hospital of Gannan Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Thyroid and Hernia Surgery, First Affiliated Hospital of Gannan Medical University","institution_ids":["https://openalex.org/I4210133784"]},{"raw_affiliation_string":"Longnan Hospital, First Affiliated Hospital of Gannan Medical University","institution_ids":["https://openalex.org/I4210133784"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5161480858"],"corresponding_institution_ids":["https://openalex.org/I4210133784"],"apc_list":{"value":3150,"currency":"CHF","value_usd":3801},"apc_paid":{"value":3150,"currency":"CHF","value_usd":3801},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"17","issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10329","display_name":"Thyroid Cancer Diagnosis and Treatment","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10329","display_name":"Thyroid Cancer Diagnosis and Treatment","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10293","display_name":"Thyroid Disorders and Treatments","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11728","display_name":"Thyroid and Parathyroid Surgery","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2746","display_name":"Surgery"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C179223381","wikidata":"https://www.wikidata.org/wiki/Q419425","display_name":"Avidity","level":3,"score":0.7968999743461609},{"id":"https://openalex.org/C2779761222","wikidata":"https://www.wikidata.org/wiki/Q826522","display_name":"Thyroid cancer","level":3,"score":0.6122999787330627},{"id":"https://openalex.org/C526584372","wikidata":"https://www.wikidata.org/wiki/Q16399","display_name":"Thyroid","level":2,"score":0.5532000064849854},{"id":"https://openalex.org/C77255625","wikidata":"https://www.wikidata.org/wiki/Q402093","display_name":"Reprogramming","level":3,"score":0.5266000032424927},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5213000178337097},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5055000185966492},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.5001000165939331},{"id":"https://openalex.org/C2776817793","wikidata":"https://www.wikidata.org/wiki/Q6553369","display_name":"Lineage (genetic)","level":3,"score":0.4580000042915344},{"id":"https://openalex.org/C83640560","wikidata":"https://www.wikidata.org/wiki/Q180951","display_name":"Chromatin","level":3,"score":0.4138999879360199},{"id":"https://openalex.org/C89611455","wikidata":"https://www.wikidata.org/wiki/Q6804646","display_name":"Mechanism (biology)","level":2,"score":0.41100001335144043},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.364300012588501},{"id":"https://openalex.org/C509974204","wikidata":"https://www.wikidata.org/wiki/Q180507","display_name":"Radiation therapy","level":2,"score":0.3555000126361847},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3424000144004822},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.337799996137619},{"id":"https://openalex.org/C148738053","wikidata":"https://www.wikidata.org/wiki/Q210861","display_name":"Cellular differentiation","level":3,"score":0.32600000500679016},{"id":"https://openalex.org/C2778835679","wikidata":"https://www.wikidata.org/wiki/Q412228","display_name":"Thyroglobulin","level":3,"score":0.31700000166893005},{"id":"https://openalex.org/C28328180","wikidata":"https://www.wikidata.org/wiki/Q48196","display_name":"Stem cell","level":2,"score":0.31619998812675476},{"id":"https://openalex.org/C2778384578","wikidata":"https://www.wikidata.org/wiki/Q16930687","display_name":"Therapeutic approach","level":3,"score":0.30140000581741333},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.29409998655319214},{"id":"https://openalex.org/C179185449","wikidata":"https://www.wikidata.org/wiki/Q219699","display_name":"Suppressor","level":3,"score":0.28630000352859497},{"id":"https://openalex.org/C2780616701","wikidata":"https://www.wikidata.org/wiki/Q1738547","display_name":"Sodium-iodide symporter","level":5,"score":0.2700999975204468},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.2696000039577484},{"id":"https://openalex.org/C41091548","wikidata":"https://www.wikidata.org/wiki/Q26939","display_name":"Epigenetics","level":3,"score":0.26170000433921814},{"id":"https://openalex.org/C7386963","wikidata":"https://www.wikidata.org/wiki/Q3954859","display_name":"Negative selection","level":4,"score":0.25949999690055847},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.2583000063896179},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.251800000667572},{"id":"https://openalex.org/C2781230642","wikidata":"https://www.wikidata.org/wiki/Q492646","display_name":"Targeted therapy","level":3,"score":0.2502000033855438}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.3389/fendo.2026.2017741","doi":"https://doi.org/10.3389/fendo.2026.2017741","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fendo.2026.2017741","pdf_url":null,"source":{"id":"https://openalex.org/S2597401208","display_name":"Frontiers in Endocrinology","issn_l":"1664-2392","issn":["1664-2392"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","ki-jl-1","medline","norway-1","oarl","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Endocrinology","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.3389/fendo.2026.2017741","doi":"https://doi.org/10.3389/fendo.2026.2017741","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fendo.2026.2017741","pdf_url":null,"source":{"id":"https://openalex.org/S2597401208","display_name":"Frontiers in Endocrinology","issn_l":"1664-2392","issn":["1664-2392"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","ki-jl-1","medline","norway-1","oarl","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Endocrinology","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":118,"referenced_works":["https://openalex.org/W1848939527","https://openalex.org/W1967624469","https://openalex.org/W1977058463","https://openalex.org/W1981910764","https://openalex.org/W1985430208","https://openalex.org/W2010437021","https://openalex.org/W2011043467","https://openalex.org/W2014746924","https://openalex.org/W2020851483","https://openalex.org/W2034083247","https://openalex.org/W2034515342","https://openalex.org/W2040642592","https://openalex.org/W2043405039","https://openalex.org/W2062536748","https://openalex.org/W2063665939","https://openalex.org/W2065003195","https://openalex.org/W2065271250","https://openalex.org/W2069740645","https://openalex.org/W2079353352","https://openalex.org/W2082832566","https://openalex.org/W2093320778","https://openalex.org/W2097038360","https://openalex.org/W2097182421","https://openalex.org/W2100242437","https://openalex.org/W2101514909","https://openalex.org/W2110113462","https://openalex.org/W2112169633","https://openalex.org/W2113637323","https://openalex.org/W2117574089","https://openalex.org/W2120775347","https://openalex.org/W2130871775","https://openalex.org/W2135807249","https://openalex.org/W2139273584","https://openalex.org/W2139518879","https://openalex.org/W2141787711","https://openalex.org/W2153057419","https://openalex.org/W2155180139","https://openalex.org/W2166568854","https://openalex.org/W2170833627","https://openalex.org/W2199669643","https://openalex.org/W2279570938","https://openalex.org/W2320378887","https://openalex.org/W2461237997","https://openalex.org/W2467366089","https://openalex.org/W2474627812","https://openalex.org/W2520304492","https://openalex.org/W2523443463","https://openalex.org/W2584298991","https://openalex.org/W2610367673","https://openalex.org/W2795875131","https://openalex.org/W2805565290","https://openalex.org/W2884254274","https://openalex.org/W2894264092","https://openalex.org/W2913630332","https://openalex.org/W2923440107","https://openalex.org/W2964573638","https://openalex.org/W2966674226","https://openalex.org/W2976988657","https://openalex.org/W2981459412","https://openalex.org/W2986934114","https://openalex.org/W3002315770","https://openalex.org/W3010398944","https://openalex.org/W3010705074","https://openalex.org/W3094538101","https://openalex.org/W3112658701","https://openalex.org/W3134124286","https://openalex.org/W3153037559","https://openalex.org/W3159027907","https://openalex.org/W3178521081","https://openalex.org/W3185057678","https://openalex.org/W3192020907","https://openalex.org/W3206346662","https://openalex.org/W3209002826","https://openalex.org/W4206658543","https://openalex.org/W4206708280","https://openalex.org/W4213337330","https://openalex.org/W4281258383","https://openalex.org/W4281639366","https://openalex.org/W4292261975","https://openalex.org/W4306957254","https://openalex.org/W4311436937","https://openalex.org/W4320484957","https://openalex.org/W4366351113","https://openalex.org/W4367297794","https://openalex.org/W4376224484","https://openalex.org/W4381714921","https://openalex.org/W4381801293","https://openalex.org/W4385751787","https://openalex.org/W4386860330","https://openalex.org/W4387861003","https://openalex.org/W4388234085","https://openalex.org/W4388302828","https://openalex.org/W4388827701","https://openalex.org/W4389303027","https://openalex.org/W4389452652","https://openalex.org/W4392970806","https://openalex.org/W4399883702","https://openalex.org/W4401206771","https://openalex.org/W4402220086","https://openalex.org/W4403302784","https://openalex.org/W4407830665","https://openalex.org/W4408103759","https://openalex.org/W4409986601","https://openalex.org/W4410098888","https://openalex.org/W4411054674","https://openalex.org/W4413267095","https://openalex.org/W4413972333","https://openalex.org/W4415620865","https://openalex.org/W4416723900","https://openalex.org/W7125206468","https://openalex.org/W7128782508","https://openalex.org/W7138929829","https://openalex.org/W7163415952","https://openalex.org/W7164746212","https://openalex.org/W7165206196","https://openalex.org/W7172487270","https://openalex.org/W7203821184","https://openalex.org/W7204447727"],"related_works":[],"abstract_inverted_index":{"Radioiodine-refractory":[0],"differentiated":[1],"thyroid":[2,244],"cancer":[3],"(RAIR-DTC)":[4],"arises":[5],"when":[6],"tumour":[7],"evolution":[8],"disrupts":[9],"the":[10,187,223],"coordinated":[11],"thyroid-follicular":[12],"program":[13],"required":[14],"for":[15,191],"radioiodine":[16],"(RAI)":[17],"uptake,":[18],"retention":[19],"and":[20,49,66,104,109,117,140,162,164,195,219],"therapeutic":[21,181],"radiation":[22,107,217],"delivery.":[23],"Pharmacological":[24],"inhibition":[25],"of":[26,40,44,89,98,135,152,235,241],"oncogenic":[27],"MAPK":[28],"signaling":[29],"has":[30],"established":[31],"that":[32,123],"this":[33,62],"loss":[34],"is":[35],"reversible":[36],"in":[37],"a":[38,87,180],"subset":[39],"tumors,":[41],"yet":[42],"restoration":[43,97,234],"RAI":[45,81,168],"avidity":[46,169,237],"remains":[47],"heterogeneous":[48],"does":[50,127],"not":[51,128],"necessarily":[52],"translate":[53],"into":[54],"tumor":[55,110,208],"control.":[56],"Rather":[57],"than":[58,179],"cataloguing":[59],"redifferentiation":[60,85,131,231],"agents,":[61],"Review":[63],"asks":[64],"where":[65],"why":[67,166],"recovery":[68,154,240],"succeeds":[69],"or":[70,201],"fails":[71],"as":[72,86,173],"tumors":[73],"progress":[74],"from":[75,155],"molecular":[76],"reprogramming":[77],"to":[78],"therapeutically":[79,242],"meaningful":[80,243],"response.":[82,111],"We":[83],"conceptualize":[84],"sequence":[88],"biologically":[90],"distinct":[91],"but":[92,126],"interconnected":[93],"transitions:":[94],"thyroid-lineage":[95],"reactivation,":[96],"functional":[99,157,176,213],"surface":[100],"NIS,":[101],"iodide":[102],"uptake":[103],"retention,":[105],"lesion-level":[106,216],"delivery":[108,218],"Each":[112],"transition":[113],"introduces":[114],"specific":[115],"bottlenecks":[116],"candidate":[118],"determinants.":[119],"Clinical":[120],"evidence":[121],"indicates":[122],"genotype":[124],"shapes,":[125],"uniquely":[129],"determine,":[130],"response,":[132,212],"whereas":[133,193],"markers":[134],"residual":[136],"differentiation,":[137],"chromatin":[138],"state":[139],"metabolic":[141],"phenotype":[142,177],"remain":[143,198],"incompletely":[144],"validated.":[145],"This":[146],"transition-based":[147],"framework":[148],"distinguishes":[149],"pretreatment":[150],"prediction":[151],"lineage":[153,211],"post-induction":[156],"selection":[158],"using":[159],"iodine":[160,214,236],"imaging":[161],"dosimetry,":[163],"explains":[165],"restored":[167],"should":[170,205],"be":[171],"regarded":[172],"an":[174],"intermediate":[175],"rather":[178],"endpoint.":[182],"MAPK-directed":[183],"therapy":[184],"currently":[185],"provides":[186],"strongest":[188],"clinical":[189,220],"foundation":[190],"redifferentiation,":[192],"chromatin-":[194],"trafficking-directed":[196],"approaches":[197],"predominantly":[199],"mechanistic":[200],"preclinical.":[202],"Future":[203],"studies":[204],"integrate":[206],"baseline":[207],"state,":[209],"dynamic":[210],"handling,":[215],"outcome":[221],"within":[222],"same":[224],"prospective":[225],"framework.":[226],"Such":[227],"integration":[228],"may":[229],"move":[230],"beyond":[232],"empirical":[233],"toward":[238],"mechanism-informed":[239],"function.":[245]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}