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Radioiodine-Refractory Thyroid Cancer: Restoring Response to Radioiodine Therapy

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Thyroid Cancer

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Abstract

Most cases of thyroid cancer can be treated effectively with total thyroidectomy, in some cases followed by adjuvant radioactive iodine (RAI) therapy. Mortality is primarily associated with metastatic disease, especially when RAI avidity is lost. There have been many efforts to develop therapies to restore the ability of RAI-refractory thyroid cancers to trap iodide and respond to this treatment. Retinoids, peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, histone deacetylase (HDAC) inhibitors, and DNA-demethylating agents have shown some activity to restore RAI uptake in vitro. However, clinical trials with these agents have shown, at best, mixed results. Papillary thyroid cancers (PTC) are associated with mutually exclusive mutations of oncogenes encoding effectors of the mitogen-activated protein kinase (MAPK) signaling pathway. The activated BRAFv600E mutation is the most frequent genetic alteration in PTC and confers patients with a poor prognosis. Inhibitors of the MAPK pathway, such as MEK inhibitors, have been shown to restore sodium-iodine symporter (NIS) expression and iodide uptake in vitro and in mouse models and are currently undergoing clinical trials with promising results.

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Authors and Affiliations

  1. Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA

    Stephanie A. Fish MD

  2. Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 296, New York, NY, 10065, USA

    James A. Fagin MD

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Correspondence to James A. Fagin MD .

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  1. Department of Medicine, MedStar Washington Hospital Center Georgetown University School of Medicine, Washington, DC, USA

    Leonard Wartofsky

  2. Nuclear Medicine Research MedStar Research Institute and Washington Hospital Center, Georgetown University School of Medicine Washington Hospital Center, Washington, DC, USA

    Douglas Van Nostrand

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Fish, S.A., Fagin, J.A. (2016). Radioiodine-Refractory Thyroid Cancer: Restoring Response to Radioiodine Therapy. In: Wartofsky, L., Van Nostrand, D. (eds) Thyroid Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3314-3_68

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  • DOI: https://doi.org/10.1007/978-1-4939-3314-3_68

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