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Spitzweg

Clinical review 132: The sodium iodide symporter and its potential role in cancer therapy.

Spitzweg C, Harrington KJ, Pinke LA, Vile RG, Morris JC.

J Clin Endocrinol Metab. 2001 Jul;86(7):3327-35. Review.

"As the thyroidal membrane protein that mediates iodide transport into thyroid follicular cells, NIS plays a key role in thyroid pathophysiology and allows very effective use of radioiodine for diagnosis and therapy of thyroid cancer. Since NIS was cloned in 1996, most studies have demonstrated decreased NIS expression levels in thyroid carcinomas, which may account at least in part for the reduced iodide uptake activity generally observed in such tumors. Initial therapeutic strategies, including RA and demethylation treatment, have been explored with the aim of stimulating NIS expression and optimizing therapeutic responsiveness to ¹³¹I in thyroid cancer.

^"Functional NIS expression has further been detected and characterized in lactating mammary gland, providing iodide to the newborn, as well as in breast cancer tissue in vitro and in vivo, suggesting that radioiodine may be a potential alternative diagnostic and therapeutic modality in breast cancer. Although a recent study using RA to stimulate functional NIS expression in breast cancer cells yielded a selective cytotoxic effect of ¹³¹I in vitro, in vivo studies are needed to confirm these findings.

"In addition, cloning and molecular analysis of the NIS gene offer the possibility of a novel cytoreductive gene therapy strategy based on targeted NIS gene transfer into nonthyroidal tumors, followed by radioiodine therapy. This novel form of gene therapy would extend the application of carrier-free radioiodine and the extensive experience with radioiodine in thyroid cancer management to the treatment of extrathyroidal tumors. If further in vivo studies using efficient and safe in vivo NIS gene delivery systems can confirm the promising preliminary results obtained in various in vitro and in vivo experiments, this approach is undoubtedly one of the most exciting chapters of NIS gene-based research since its cloning in 1996.^"

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