甲状腺癌碘-131治疗抵抗发生的分子机制研究进展

doi:10.3969/j.issn.1674-8115.2024.07.013

上海交通大学学报（医学版） ›› 2024, Vol. 44 ›› Issue (7): 915-921.doi: 10.3969/j.issn.1674-8115.2024.07.013

• 综述 • 上一篇

甲状腺癌碘-131治疗抵抗发生的分子机制研究进展

刘诗琪¹(), 王辉¹, 冯方²()

^1.上海交通大学医学院附属新华医院核医学科，上海 200092
^2.同济大学附属上海市第四人民医院核医学科，上海 200434

收稿日期:2024-03-11 接受日期:2024-04-10 出版日期:2024-07-28 发布日期:2024-07-28
通讯作者: 冯方 E-mail:lsq0617@sjtu.edu.cn;2305120@tongji.edu.cn
作者简介:刘诗琪（1999—），女，硕士生；电子信箱：lsq0617@sjtu.edu.cn。
基金资助:
国家自然科学基金(81974269);上海交通大学“交大之星”计划医工交叉研究基金(YG2019QNA39)

Advances in molecular mechanisms of iodine-131 therapy resistance in thyroid carcinoma

LIU Shiqi¹(), WANG Hui¹, FENG Fang²()

^1.Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
^2.Department of Nuclear Medicine, Shanghai Fourth People′s Hospital, Tongji University, Shanghai 200434, China

Received:2024-03-11 Accepted:2024-04-10 Online:2024-07-28 Published:2024-07-28
Contact: FENG Fang E-mail:lsq0617@sjtu.edu.cn;2305120@tongji.edu.cn
Supported by:
National Natural Science Found of China(81974269);Biomedical-engineering Cross Fund of Shanghai Jiao Tong University(YG2019QNA39)

摘要/Abstract

摘要：

甲状腺癌是内分泌系统最常见的恶性肿瘤，其中分化型甲状腺癌（differentiated thyroid carcinoma，DTC）占90%以上。多数DTC患者经过系统治疗后预后良好，但少数患者肿瘤原发灶或转移灶出现失分化现象，进展为放射性碘难治性DTC（radioiodine-refractory DTC，RAIR-DTC），预后明显变差，是甲状腺癌致死的主要原因。钠碘转运体（sodium iodide symporter，NIS）的表达和功能异常，是导致甲状腺癌碘-131治疗抵抗的主要原因，其发生受遗传学改变、表观遗传学改变、肿瘤微环境作用、自噬作用等多因素影响。遗传学改变如BRAF基因的V600E位点突变、RET/PTC基因重排等导致致癌信号通路的激活，直接或间接地影响NIS的表达及其在细胞膜上的正常定位。表观遗传学调控特定基因的表达模式，调节NIS的表达水平，进而影响甲状腺细胞的碘摄取功能。肿瘤微环境中的免疫细胞、细胞因子和细胞外基质等成分也可能通过降低NIS的表达水平和/或干扰其在细胞膜上的正常功能导致细胞碘摄取障碍。此外，自噬作为一种细胞内部的代谢调节机制，也可以调节NIS的表达及其在细胞内的分布，从而影响碘的摄取和碘-131治疗的敏感性。通过综述以上因素在甲状腺癌失分化中的作用机制，可以更全面地理解RAIR-DTC的发生和发展过程，有助于探寻新的治疗靶点，改善预后，并为患者提供更有效的个体化治疗策略。

关键词: 分化型甲状腺癌, 失分化, 放射性碘, 钠碘转运体

Abstract:

Thyroid cancer is the most common malignant tumor of the endocrine system, with differentiated thyroid carcinoma (DTC) accounting for over 90%. Most DTC patients have a good prognosis after systematic treatment, but a few develop dedifferentiation of primary tumor site or metastases, progressing to radioiodine-refractory DTC (RAIR-DTC), leading to significantly worse prognosis, which is a major cause of thyroid carcinoma-related mortality. Dysregulation of sodium iodide symporter (NIS) expression and function is the main reason for iodine-131 therapy resistance in thyroid carcinoma, influenced by genetic changes, epigenetic changes, tumor microenvironment, autophagy, and other factors. Genetic alterations such as the BRAF^V600E mutation and RET/PTC chromosomal rearrangements activate oncogenic signaling pathways, directly or indirectly affecting NIS expression and its normal localization on the cell membrane. Epigenetic regulation modulates specific gene expression patterns, regulating NIS gene expression levels, thereby affecting the radioiodine uptake function of thyroid cells. Components in the tumor microenvironment, including immune cells, cytokines, and extracellular matrix, may also disrupt iodine uptake by reducing the expression levels of NIS and/or disrupting its normal function on the cell membrane. Additionally, autophagy, as an intracellular metabolic regulatory mechanism, can also modulate NIS expression and its intracellular distribution, thus impacting the radioiodine uptake and the sensitivity to iodine-131 therapy. Reviewing the roles of these factors in thyroid carcinoma dedifferentiation comprehensively can provide a more thorough understanding of the occurrence and progression of RAIR-DTC, aiding in the exploration of new therapeutic targets, improving prognosis, and providing more effective personalized treatment strategies for patients.

Key words: differentiated thyroid carcinoma, dedifferentiation, radioiodine, sodium iodide symporter

中图分类号:

R736.1

刘诗琪, 王辉, 冯方. 甲状腺癌碘-131治疗抵抗发生的分子机制研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(7): 915-921.

LIU Shiqi, WANG Hui, FENG Fang. Advances in molecular mechanisms of iodine-131 therapy resistance in thyroid carcinoma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(7): 915-921.

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甲状腺癌碘-131治疗抵抗发生的分子机制研究进展

Advances in molecular mechanisms of iodine-131 therapy resistance in thyroid carcinoma

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