Molecular basis and targeted therapies for radioiodine refractory thyroid cancer |
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Authors: | Qiuxiao Yu Xuwen Zhang Li Li Chi Zhang Jian Huang Wenting Huang |
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Affiliation: | Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, P. R. China |
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Abstract: | Patients diagnosed with radioiodine refractory thyroid cancer (RAIR-TC) are not amenable to novel 131I therapy due to the reduced expression of sodium iodide symporter (Na+/I- symporter, NIS) and/or the impairment of NIS trafficking to the plasma membrane. RAIR-TC patients have a relatively poor prognosis with a mean life expectancy of 3–5 years, contributing to the majority of TC-associated mortality. Identifying RAIR-TC patients and selecting proper treatment strategies remain challenging for clinicians. In this review, we demonstrate the updated clinical scenarios or the so-called “definitions” of RAIR-TC suggested by several associations based on 131I uptake ability and tumor response post-131I therapy. We also discuss current knowledge of the molecular alterations involved in membrane-localized NIS loss, which provides a preclinical basis for the development of targeted therapies, in particular, tyrosine kinase inhibitors (TKIs), redifferentiation approaches, and immune checkpoint inhibitors. |
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Keywords: | immune checkpoint inhibitors radioiodine refractory thyroid cancer redifferentiation therapies sodium/iodide symporter tyrosine kinase inhibitors |
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