Progress and prospect on treatment for radioiodine-refractory thyroid cancer

Most patients with differentiated thyroid cancer benefit from surgery, radioactive iodine-131 therapy and TSH suppression therapy, resulting in a favorable prognosis. However, once radioactive iodine refractory thyroid cancer (RAIR-DTC) develops, the prognosis becomes significantly poorer, treatment...

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Main Author: GENG Qianqian, YANG Aimin
Format: Article
Language:English
Published: Editorial Office of China Oncology 2025-01-01
Series:Zhongguo aizheng zazhi
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Online Access:http://www.china-oncology.com/fileup/1007-3639/PDF/1739775845187-2003910516.pdf
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author GENG Qianqian, YANG Aimin
author_facet GENG Qianqian, YANG Aimin
author_sort GENG Qianqian, YANG Aimin
collection DOAJ
description Most patients with differentiated thyroid cancer benefit from surgery, radioactive iodine-131 therapy and TSH suppression therapy, resulting in a favorable prognosis. However, once radioactive iodine refractory thyroid cancer (RAIR-DTC) develops, the prognosis becomes significantly poorer, treatment options are limited, and therapeutic efficacy is constrained. This has emerged as a research focus in recent years. With advancements in understanding tumor mechanisms and rapid developments in diagnostic and therapeutic technologies, significant progress has been made in new drugs and new treatments for RAIR-DTC. The development of novel targeted therapies has revolutionized the management. Notably, multi-target tyrosine kinase inhibitor (mTKI) such as sorafenib and lenvatinib has demonstrated significant improvements in progression-free survival, thereby establishing targeted therapy as a viable option for RAIR-DTC. Cabozantinib has also shown promising results as a second-line treatment following TKI failure. Other TKIs like apatinib and anlotinib have also arnered attention due to efficacy and safety. Additionally, specific TKI targeting BRAF V600E mutations, RET fusions and NTRK fusion genes have ushered in an era of precision medicine for RAIR-DTC. Thus, for patients with RET or NTRK fusions, guidelines recommend prioritizing specific target TKI over pan-target kinase inhibitors. If no such gene mutations are present, pan-target kinase inhibitors are considered as the standard first-line treatments. MEK inhibitors (selumetinib) may induce redifferentiation, potentially restoring iodine uptake. Consequently, the combination of targeted therapy and iodine-131 therapy represents a promising strategy. While immune checkpoint inhibitors only have not yielded optimistic results in RAIR-DTC, combination with TKIs has shown certain safety and efficacy, warranting further exploration. However, given issues of drug resistance and intolerable side effects, it is imperative to explore new treatments. Radionuclide therapy guided by nuclear medicine molecular imaging offers potential hope for RAIR-DTC patients. Targeted radioligand/receptor therapies, such as PSMA, SSTR and FAPi, exhibit characteristics of targeting, visualization and integration of diagnosis and treatment. Initial trials of them in RAIR-DTC patients with TKIs treatment failure have been confirmed feasibility. This review summarized recent advances in new drugs and new technologies for RAIR-DTC treatment, aiming to guide clinical practice and anticipate more personalized and precise treatment options to improve quality of life and survival.
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spelling doaj-art-e1569b6fa9c148de9a7aacaecf34539e2025-08-20T01:50:45ZengEditorial Office of China OncologyZhongguo aizheng zazhi1007-36392025-01-01351303910.19401/j.cnki.1007-3639.2025.01.004Progress and prospect on treatment for radioiodine-refractory thyroid cancerGENG Qianqian, YANG Aimin0Department of Nuclear Medicine, The first affiliated hospital of Xi’an Jiao Tong University, Xi’an 710061, Shaanxi Province, ChinaMost patients with differentiated thyroid cancer benefit from surgery, radioactive iodine-131 therapy and TSH suppression therapy, resulting in a favorable prognosis. However, once radioactive iodine refractory thyroid cancer (RAIR-DTC) develops, the prognosis becomes significantly poorer, treatment options are limited, and therapeutic efficacy is constrained. This has emerged as a research focus in recent years. With advancements in understanding tumor mechanisms and rapid developments in diagnostic and therapeutic technologies, significant progress has been made in new drugs and new treatments for RAIR-DTC. The development of novel targeted therapies has revolutionized the management. Notably, multi-target tyrosine kinase inhibitor (mTKI) such as sorafenib and lenvatinib has demonstrated significant improvements in progression-free survival, thereby establishing targeted therapy as a viable option for RAIR-DTC. Cabozantinib has also shown promising results as a second-line treatment following TKI failure. Other TKIs like apatinib and anlotinib have also arnered attention due to efficacy and safety. Additionally, specific TKI targeting BRAF V600E mutations, RET fusions and NTRK fusion genes have ushered in an era of precision medicine for RAIR-DTC. Thus, for patients with RET or NTRK fusions, guidelines recommend prioritizing specific target TKI over pan-target kinase inhibitors. If no such gene mutations are present, pan-target kinase inhibitors are considered as the standard first-line treatments. MEK inhibitors (selumetinib) may induce redifferentiation, potentially restoring iodine uptake. Consequently, the combination of targeted therapy and iodine-131 therapy represents a promising strategy. While immune checkpoint inhibitors only have not yielded optimistic results in RAIR-DTC, combination with TKIs has shown certain safety and efficacy, warranting further exploration. However, given issues of drug resistance and intolerable side effects, it is imperative to explore new treatments. Radionuclide therapy guided by nuclear medicine molecular imaging offers potential hope for RAIR-DTC patients. Targeted radioligand/receptor therapies, such as PSMA, SSTR and FAPi, exhibit characteristics of targeting, visualization and integration of diagnosis and treatment. Initial trials of them in RAIR-DTC patients with TKIs treatment failure have been confirmed feasibility. This review summarized recent advances in new drugs and new technologies for RAIR-DTC treatment, aiming to guide clinical practice and anticipate more personalized and precise treatment options to improve quality of life and survival.http://www.china-oncology.com/fileup/1007-3639/PDF/1739775845187-2003910516.pdf|radioactive iodine refractory|differentiated thyroid cancer|targeted therapy|immunotherapy|radionuclide therapy|tyrosine kinase inhibitor
spellingShingle GENG Qianqian, YANG Aimin
Progress and prospect on treatment for radioiodine-refractory thyroid cancer
Zhongguo aizheng zazhi
|radioactive iodine refractory|differentiated thyroid cancer|targeted therapy|immunotherapy|radionuclide therapy|tyrosine kinase inhibitor
title Progress and prospect on treatment for radioiodine-refractory thyroid cancer
title_full Progress and prospect on treatment for radioiodine-refractory thyroid cancer
title_fullStr Progress and prospect on treatment for radioiodine-refractory thyroid cancer
title_full_unstemmed Progress and prospect on treatment for radioiodine-refractory thyroid cancer
title_short Progress and prospect on treatment for radioiodine-refractory thyroid cancer
title_sort progress and prospect on treatment for radioiodine refractory thyroid cancer
topic |radioactive iodine refractory|differentiated thyroid cancer|targeted therapy|immunotherapy|radionuclide therapy|tyrosine kinase inhibitor
url http://www.china-oncology.com/fileup/1007-3639/PDF/1739775845187-2003910516.pdf
work_keys_str_mv AT gengqianqianyangaimin progressandprospectontreatmentforradioiodinerefractorythyroidcancer