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Endocrine Abstracts (2019) 63 S1.2 | DOI: 10.1530/endoabs.63.S1.2

ECE2019 Symposia Thyroid in cancer (3 abstracts)

Iodine refractoriness in thyroid cells

Chris McCabe



The ability of thyroid cells to specifically uptake radioiodine is frequently compromised in the neoplastic setting, particularly in older patients with poorly differentiated thyroid cancer and larger metastases, resulting in a 10-year survival rate of less than 10%. The mechanisms which govern cellular iodide uptake via the sodium iodide symporter (NIS) have been elucidated with increasing molecular clarity over the past 35 years. NIS is regulated in a tissue-specific manner, and its correct functioning is sensitive to an incredibly wide array of regulatory events, from the genetic to the epigenetic, via miRNAs and lncRNAs, as well as transcription factors, hormones and growth factors, and is particularly at the mercy of activated kinase pathways. New mechanisms regulating NIS activity continue to be identified, shining fresh light on the ways in which thyroid cells become refractory to iodide uptake, particularly in aggressive thyroid cancer. This considerable experimental endeavour is currently driving ongoing clinical trials aimed at overcoming iodine refractoriness, with the consensus view that single agent approaches may not be sufficient to boost NIS function for effective therapy. To this end, new insight into how NIS is intracellularly trafficked and targeted to the plasma membrane is emerging, which may transform our understanding of how to ultimately address iodine refractoriness. Thus combinatorial approaches targeting key components of NIS repression and mislocalisation may finally be able to overcome the iodine refractoriness which is a hallmark of dedifferentiated thyroid cancer, opening the possibility of effective treatment to patients who currently cannot uptake sufficient radioiodine for tumour cell ablation.

Volume 63

21st European Congress of Endocrinology

Lyon, France
18 May 2019 - 21 May 2019

European Society of Endocrinology 

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