Work

Molecular Mechanisms of Radioiodine Refractoriness in Differentiated Thyroid Cancer: Focus on Sodium/Iodide Symporter Dysregulation

Year: 2026

Type: article

Abstract: The sodium/iodide symporter (NIS/SLC5A5) is a major determinant of radioiodine therapy efficacy in differentiated thyroid cancer (DTC). This narrative review examines the molecular mechanisms underlying NIS dysregulation and radioiodine refractoriness in DTC. Reduced NIS expression or function in radioiodine-refractory DTC is associated with multiple mechanisms, including transcriptional suppression linked to MAPK/ERK and PI3K/AKT pathway activation and disruption of thyroid differentiation programs; epigenetic silencing involving SLC5A5 regulatory regions; impaired protein trafficking and membrane localization; and post-transcriptional regulation by microRNAs such as miR-221-3p, miR-222-3p, miR-146b-3p, and miR-204-5p. Genetic alterations including BRAF V600E and TERT promoter mutations are associated with dedifferentiated tumor phenotypes and poor radioiodine response. Redifferentiation approaches using MAPK pathway inhibitors such as selumetinib and dabrafenib can restore iodine uptake in selected patients, although the overall clinical applicability of these strategies remains under evaluation. A better understanding of these mechanisms may support improved biologic stratification and more selective therapeutic decision-making in radioiodine-refractory DTC.

Source: Current Issues in Molecular Biology

DOI: 10.3390/cimb48040362

Authors: Vladimir D. Rokashkov, Liudmila V. Spirina, Natalya V. Tarasenko, Svetlana Yu. Chizhevskaya

Institutions: Siberian State Medical University, Russian Academy of Sciences, Tomsk National Research Medical Center, Tomsk Cancer Research Institute

Language: English

Topic: Thyroid Cancer Diagnosis and Treatment

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,654