Molecular reasons why some thyroid cancers resist radioactive iodine: Reduced iodine transporter levels caused by changes in cell signals and location

Advanced, metastatic differentiated thyroid cancers (DTCs) are associated with a poor prognosis due to radioactive iodine refractoriness.

• Decreased expression and improper targeting of the sodium iodide symporter (NIS) contribute to the failure of radioactive iodine (RAI) therapy.
• Genetic changes, including RET/PTC rearrangements, are linked to the onset and progression of DTCs.
• Activation of specific signaling pathways, such as MAPK and PI3K/AKT, is involved in the dedifferentiation of DTCs.
• These molecular alterations lead to reduced NIS levels and impaired RAI uptake, resulting in resistance to therapy.
• Various preclinical approaches have shown promise in restoring NIS expression and improving RAI uptake.

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