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Molecular mechanisms of radioactive iodine refractoriness in differentiated thyroid cancer: Impaired sodium iodide symporter (NIS) expression owing to altered signaling pathway activity and intracellular localization of NIS

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Oh, Ji Min, Ahn, Byeong-Cheol·2021·Theranostics
DOI 10.7150/thno.57689PMC PMC8120202
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Abstract

, and RET/PTC rearrangements) have been reported to be prominently responsible for the onset, progression, and dedifferentiation of DTCs, mainly through the activation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Eventually, these alterations result in a lack of NIS and disabling of RAI uptake, leading to the development of resistance to RAI therapy. Over the past decade, promising approaches with various targets have been reported to restore NIS expression and RAI uptake in preclinical studies. In this review, we summarized comprehensive molecular mechanisms underlying the dedifferentiation in RAI-refractory DTCs and reviews strategies for restoring RAI avidity by tackling the mechanisms.

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  • Dedifferentiation and development of radioactive iodine refractory diseases, resulting from decreased thyroid differentiation factors especially NIS, is a leading cause for BRAFV600E-related poor prognosis and mortality in thyroid tumorigenesis.

    “Dedifferentiation and development of radioactive iodine (RAI) refractory diseases, resulted from decreased thyroid differentiation factors, especially sodium iodide symporter (NIS), is also the leading cause for BRAFV600E-related poor prognosis and mortality in thyroid tumorigenesis28–30.”

    From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [28]

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Authors
Oh, J. M., & Ahn, B.-C.
Affiliations
Kyungpook National University Hospital (KR)
Corresponding author
Ahn, Byeong-Cheol
ORCID
Venue
Theranostics
Publisher
Ivyspring International Publisher
Published
2021
Volume
11
Issue
13
Pages
6251-6277
ISSN
1838-7640 (ISSN-L)
DOI
10.7150/thno.57689
PMC
PMC8120202
OpenAlex
W3159027907
Cited by
163
References
2
Citations by year
2026: 41 · 2025: 35 · 2024: 28 · 2023: 30 · 2022: 22 · 2021: 6
FWCI
16.80
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Theranostics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
Keywords
differentiated thyroid cancer, sodium iodide symporter, NIS expression, dedifferentiation, RET/PTC rearrangement, MAPK signaling, PI3K/Akt signaling, radioiodine uptake
MeSH terms
Sodium-Iodide Symporters, Autophagy, Cell Differentiation, Cell Membrane, Clinical Trials as Topic, Humans, Iodine Radioisotopes, Neoplasm Proteins, Receptors, Thyrotropin, Recombinant Proteins, Thyroid Neoplasms, Thyrotropin, Genetic Therapy, Signal Transduction, Gene Expression Regulation, Neoplastic, Salvage Therapy, Receptors, Cytoplasmic and Nuclear, Drug Resistance, Neoplasm, Protein Transport, Symporters, MicroRNAs, Epigenesis, Genetic

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