Molecular basis and targeted therapies for radioiodine refractory thyroid cancer,Asia-Pacific Journal of Clinical Oncology

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Molecular basis and targeted therapies for radioiodine refractory thyroid cancer
Asia-Pacific Journal of Clinical Oncology ( IF 1.4 ) Pub Date : 2022-08-10 , DOI: 10.1111/ajco.13836
Qiuxiao Yu ₁ , Xuwen Zhang ₁ , Li Li ₁ , Chi Zhang ₁ , Jian Huang ₁ , Wenting Huang ₁

Affiliation

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.

中文翻译：

放射性碘难治性甲状腺癌的分子基础和靶向治疗

由于碘化钠同向转运体（Na+/I- 同向转运体，NIS）的表达减少和/或 NIS 转运至质膜的损伤，诊断为放射性碘难治性甲状腺癌 ( RAIR-TC) 的患者不适合新型¹³¹ I 疗法. RAIR-TC 患者的预后相对较差，平均预期寿命为 3-5 年，导致大多数 TC 相关死亡率。识别 RAIR-TC 患者并选择合适的治疗策略对临床医生来说仍然具有挑战性。在这篇综述中，我们展示了几个协会根据¹³¹ I 摄取能力和^{131后肿瘤反应建议的 RAIR-TC 的更新临床情景或所谓“定义”}我治疗。我们还讨论了与膜局部 NIS 丢失有关的分子改变的当前知识，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。

更新日期：2022-08-10

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