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

Oh, Ji Min; Ahn, Byeong-Cheol

doi:10.7150/thno.57689



Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

Nanotheranostics

International Journal of Biological Sciences

International Journal of Medical Sciences

Journal of Cancer

Global reach, higher impact

Full Text | PDF

Theranostics 2021; 11(13):6251-6277. doi:10.7150/thno.57689 This issue Cite

Review

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

Ji Min Oh^1,2, Byeong-Cheol Ahn^1,2,3✉

1. Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
2. Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.
3. BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Citation:

Oh JM, Ahn BC. 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. Theranostics 2021; 11(13):6251-6277. doi:10.7150/thno.57689. https://www.thno.org/v11p6251.htm

Other styles

Abstract

The advanced, metastatic differentiated thyroid cancers (DTCs) have a poor prognosis mainly owing to radioactive iodine (RAI) refractoriness caused by decreased expression of sodium iodide symporter (NIS), diminished targeting of NIS to the cell membrane, or both, thereby decreasing the efficacy of RAI therapy. Genetic aberrations (such as BRAF, RAS, 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.

Keywords: radioactive iodine refractory thyroid cancer, redifferentiation, signaling pathways, sodium iodide symporter, membrane targeting

Citation styles

APA

Oh, J.M., Ahn, B.C. (2021). 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. Theranostics, 11(13), 6251-6277. https://doi.org/10.7150/thno.57689.

ACS

Oh, J.M.; Ahn, B.C. 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. Theranostics 2021, 11 (13), 6251-6277. DOI: 10.7150/thno.57689.

NLM

CSE

Oh JM, Ahn BC. 2021. 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. Theranostics. 11(13):6251-6277.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.