Molecular basis and targeted therapies for radioiodine refractory thyroid cancer
Molecular basis and targeted therapies for radioiodine refractory thyroid cancer
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DOI：
10.1111/ajco.13836
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发表时间：
2022-08
期刊：
影响因子：
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通讯作者：
Qiuxiao Yu;Xuwen Zhang;Li Li-Li;Chi-zhi Zhang;Jian Huang;Wenting Huang
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作者：
Qiuxiao Yu;Xuwen Zhang;Li Li-Li;Chi-zhi Zhang;Jian Huang;Wenting Huang
由于碘化钠同向转运体（Na+/I-同向转运体，NIS）表达减少和/或 NIS 向质膜运输受损，诊断为放射性碘难治性甲状腺癌 (RAIR-TC) 的患者不适合新型 131I 治疗。 RAIR-TC 患者的预后相对较差，平均预期寿命为 3-5 年，是大多数 TC 相关死亡率的原因。识别 RAIR-TC 患者并选择适当的治疗策略对临床医生来说仍然是一个挑战。在这篇综述中，我们展示了多个协会根据 131I 摄取能力和 131I 治疗后肿瘤反应提出的最新临床情况或所谓的 RAIR-TC“定义”。我们还讨论了与膜局部 NIS 丢失相关的分子改变的最新知识，这为靶向治疗的开发提供了临床前基础，特别是酪氨酸激酶抑制剂 (TKI)、再分化方法和免疫检查点抑制剂。
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.