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Comment
. 2024 Apr 1;30(7):1220-1222.
doi: 10.1158/1078-0432.CCR-23-3503.

A New Twist on a Classic: Enhancing Radioiodine Uptake in Advanced Thyroid Cancer

Melissa G Lechner  1   2 , Gregory A Brent  1   2
Affiliations
Comment

A New Twist on a Classic: Enhancing Radioiodine Uptake in Advanced Thyroid Cancer

Melissa G Lechner et al. Clin Cancer Res. .

Abstract

Advanced differentiated thyroid cancer that is resistant to radioactive iodine therapy may become responsive with a unique treatment combination of chloroquine and vorinostat. This treatment was demonstrated in cellular and animal models of thyroid cancer to inhibit endocytosis of the plasma membrane-bound iodine transporter, NIS, and restore iodine uptake. See related article by Read et al., p. 1352.

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Conflict of interest statement

Disclosure: The authors report no conflict of interest.

Figures

Figure
Figure
Iodine transport in the thyroid is mediated by the integral membrane glycoprotein, sodium iodide symporter (NIS), which transports iodine, coupled with two Na+, down the sodium gradient, high extracellular to low intracellular. The normal thyroid gland can be imaged by oral administration of radioactive iodine (RAI). The heterotrimeric AP2 adaptor complex (comprised of α1, μ2, and σ2 subunits) is a binding partner of NIS that mediates its endocytosis via clathrin-coated vesicles. AP2 is overexpressed in RAI-resistant differentiated thyroid cancer, RAIR-DTC, and is associated with reduced iodine uptake into metastatic disease. Chloroquine disrupts the interaction of AP2 and NIS, reduces NIS endocytosis and permits greater concentration of radioiodine in thyroid cancer metastases. (Figure created with BioRender.com.)
See this image and copyright information in PMC

Comment on

References

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