REVIEW article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1644562
This article is part of the Research TopicNational Cancer Research Month 2025: Advances in Detection, Treatment and Therapies in OncologyView all 13 articles
High risk factors, molecular features and clinical management for radioactive iodine-refractory differentiated thyroid carcinoma
Provisionally accepted
- Sichuan University, Chengdu, China
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Despite the generally favorable prognosis of differentiated thyroid carcinoma (DTC) following surgery and radioactive iodine (RAI) therapy, approximately 10% of cases eventually develop resistance to RAI. This condition, known as radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), is associated with a poor prognosis, with a 10-year survival rate of only 10% from the time of metastasis detection. The limited availability of safe and effective alternative treatments poses a significant challenge to clinical management. However, early identification and intervention targeting high-risk factors are critical for preventing disease progression. Integrating current insights into DTC pathogenesis with established clinical strategies offers valuable opportunities to inform the development of novel therapies and improve patient outcomes. Hence, in this review, we first examine high-risk predictors of RAIR, including demographic factors (e.g., age, sex), gene mutations (e.g., RAS, BRAF, TERT), high-risk histopathological subtypes (e.g., extrathyroidal extension and the tall cell variant), and serum biomarkers (e.g., thyroglobulin and Cyfra 21.1), all of which are widely recognized for monitoring and risk stratification. Notably, we also emphasize that inappropriate pharmacological management of comorbidities-such as diabetes, myeloid leukemia, and hypertension-may suppress sodiumiodide symporter (NIS) expression and RAI uptake, thereby contributing to RAIR development. We then summarize the molecular mechanisms underlying impaired NIS expression and function in RAIR-DTC, followed by a discussion of recent advances in clinical treatment, focusing on the efficacy and safety of both approved and investigational therapeutic agents.Thyroid carcinoma (TC) is the most common malignancy of the endocrine system and is categorized into three main histological subtypes: differentiated thyroid carcinoma (DTC), which includes both well-differentiated and poorly differentiated forms (PDTC); undifferentiated carcinoma, known as anaplastic thyroid carcinoma (ATC); and medullary thyroid carcinoma, which arises from calcitonin-producing C-cells. Among these, DTC is the most prevalent, accounting for over 90% of all TC cases(1, 2), and comprises papillary thyroid carcinoma (PTC),
Keywords: Radioiodine refractory differentiated thyroid carcinoma (RAIR-DTC), Sodium iodide symporter (NIS), High risk factors, molecular pathogenesis, Clinical management.
Received: 10 Jun 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Ma, Xie, Long and Ye. This is an open-access 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) or licensor 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.
* Correspondence: Feng Ye, Sichuan University, Chengdu, China
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