MAPK pathway inhibitors enhance radioiodine sensitivity in anaplastic thyroid carcinoma through promoting NIS expression and ARF4-mediated NIS membrane transport.

ABSTRACT: Anaplastic thyroid cancer (ATC) patient develops resistance to radioactive iodine (RAI) due to diminished sodium-iodide symporter (NIS) expression and mislocalization to the cell membrane. MAPK pathway inhibitors have demonstrated efficacy in enhancing RAI avidity in radioiodine-refractory papillary thyroid carcinoma and ATC. Elucidating this mechanism may lead to novel therapeutic approaches for ATC treatment. The cytotoxic effects of three MAPK pathway inhibitors (selumetinib, vemurafenib, dabrafenib) were assessed in ATC cell lines and xenograft models via viability assays and ¹⁸F-FDG PET/CT. We investigated their impact on radioiodine metabolism by analyzing the expression of key genes (NIS, TSHR, and TPO) and trafficking regulators (ARF4, PIGU, and β-catenin) via Western bl

SUBMITTER: Wang J 

PROVIDER: S-EPMC13473092 | biostudies-literature | 2026 Jun

REPOSITORIES: biostudies-literature