Endocrine Abstracts

Thyroid cancer is frequently treated by surgery, followed by administration of radioiodide, an ablative treatment utilising high energy beta-emitting ¹³¹I. Given that the sodium iodide symporter (NIS) is the sole transporter of iodide into human cells, and is expressed predominantly in the thyroid, ¹³¹I therapy selectively targets post-surgical thyroid remnants and metastases, markedly improving outcome and survival. Radioiodine therapy is thus a safe, specific, well tolerated and effective treatment. However, around a third of thyroid cancer patients with locoregional or distant metastases have disease that does not concentrate sufficient ¹³¹I to achieve therapeutic benefit. The 10 year survival rate is ~56% for patients with sufficient ¹³¹I uptake, but only ~10% for patients who are radioiodide resistant. Therefore in the central clinical area in which NIS is exploited, there is a pressing need for improved therapy. Over the past 10 years we have forged unique insights into the intracellular trafficking and processing of NIS, and have pioneered efforts to systemically enhance NIS function at the plasma membrane (PM) in vivo. We have now identified 2 different systemic drug approaches which significantly enhance the function of NIS in mice, by targeting (i) the rate of endocytosis of NIS within the thyroid, and (ii) the expression and proteasomal degradation of NIS. To offer future hope to patients with aggressive thyroid cancer, we now need to progress systemic strategies such as these to clinical trials so that NIS function can be enhanced at the time of radioiodine therapy, eliciting improved tumour and metastatic cell ablation.