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Review
. 2025 Jan;87(1):1-10.
doi: 10.1007/s12020-024-04018-5. Epub 2024 Sep 4.

An update on redifferentiation strategies for radioactive iodine-refractory differentiated thyroid carcinoma

Theodora Pappa  1   2   3   4 , Lori Wirth  5   6   7
Affiliations
Review

An update on redifferentiation strategies for radioactive iodine-refractory differentiated thyroid carcinoma

Theodora Pappa et al. Endocrine. 2025 Jan.

Abstract

Purpose: Although most patients with differentiated thyroid carcinoma (DTC) have an excellent prognosis, a subset will experience radioactive iodine refractory (RAI-R) disease, associated with recurrence, distant metastases and worse prognosis. In recent years, redifferentiation has emerged as an attractive approach for patients with RAI-R DTC, a strategy to induce iodine uptake in RAI-R DTC tumor cells and ultimately prolong time to initiation of systemic therapy.

Methods: An overview and critical appraisal of the existing literature on redifferentiation will be presented in this review under the lens of the genotype-specific targeted therapy administered with redifferentiation intent.

Results/conclusions: Due to the significant heterogeneity across studies, it will be key to harmonize research methodology and support future larger, multicenter prospective trials in order to identify the most suitable candidates for this therapeutic strategy.

Keywords: Differentiated thyroid carcinoma; Radioactive iodine; Radioactive iodine refractory; Redifferentiation strategy; Systemic therapy; Theranostics.

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Conflict of interest statement

Compliance with ethical standards. Conflict of interest: The authors declare no competing interests.

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