The role of thyroidal transport in the treatment of thyroid cancer is difficult to overestimate. For over 60 years, the administration of radioiodide to thyroid cancer patients after thyroidectomy has been the most effective internal targeted anticancer radiotherapy available, on account of the unique specificity of NIS. Radioiodide therapy is not only effective and specific, it is also remarkably free of severe side effects. This article shows how, upon isolation of the NIS cDNA and the characterization of the NIS molecule, considerable strides have been made in our understanding of NIS regulation at all levels, including biosynthesis, biogenesis, half-life, targeting, and subcellular localization. These advances considerably increase our potential ability to manipulate the system to optimize the effectiveness of radioiodide treatment. In addition, the discovery that NIS is expressed endogenously in breast cancer has raised, for the first time, the realistic prospect of effectively applying radioiodide therapy in extrathyroidal cancers that express NIS endogenously. Finally, recent studies on the transfer of the NIS gene to cancers that otherwise lack endogenous NIS expression, have opened the door to the possible use of radioiodide therapy in these cancers as well.
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