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碘难治性分化型甲状腺癌的治疗进展及展望
Progress and prospect on treatment for radioiodine-refractory thyroid cancer
- 中国癌症杂志 2025年35卷第1期 页码：30-39
- 作者机构：
西安交通大学第一附属医院核医学科，陕西 西安 710061
- 作者简介：
[ "耿倩倩（ORCID: 0009-0009-2137-7070），博士，副主任医师。" ]
[ "杨爱民，西安交通大学第一附属医院核医学科主任、核医学科系主任，二级主任医师、教授、博士研究生导师。中国临床肿瘤学会核医学专家委员会候任主任委员，中国医师协会核医学医师分会常委，中国抗癌协会肿瘤核医学专业委员会常委，中国临床肿瘤学会甲状腺癌专家委员会常委，中国影像技术研究会核医学分会常务委员，中国医师协会核医学分会委员、组织工作委员会委员、继续教育学组委员，中华医学会核医学分会学科建设工作委员会委员、学科技术与继续教育学组委员、医保政策工作委员会委员，陕西省医师协会核医学医师分会会长，陕西省住院医师规范化培训专家指导委员会核医学组长，陕西省医学传播学会核医学专业委员会会长，陕西省核医学与分子影像学会副主任委员，全国高等院校本科临床医学专业国际化教育十三五规划教材编写指导委员会委员，《中华核医学与分子影像杂志》《国际放射医学核医学杂志》通讯编委，国家自然科学基金一审评委。近年来主持国家自然科学基金面上项目2项，省部级课题9项；发表学术论文70余篇，其中在SCI收录期刊上发表20余篇，参编行业指南、专家共识7部。参与全国临床多中心研究3项，新药多纳非尼临床研究1项。获得省部级科技进步二等奖3项。主编、参编教育部面向二十一世纪核医学教材专著等5 部。" ]
- 基金信息：
DOI：10.19401/j.cnki.1007-3639.2025.01.004
中图分类号： R736.1收稿：2024-12-11，
修回：2025-01-21，
纸质出版：2025-01-30
- 稿件说明：
移动端阅览
耿倩倩, 杨爱民. 碘难治性分化型甲状腺癌的治疗进展及展望[J]. 中国癌症杂志, 2025,35(1):30-39.
Qianqian GENG, Aimin YANG. Progress and prospect on treatment for radioiodine-refractory thyroid cancer[J]. China Oncology, 2025, 35(1): 30-39.
耿倩倩, 杨爱民. 碘难治性分化型甲状腺癌的治疗进展及展望[J]. 中国癌症杂志, 2025,35(1):30-39. DOI： 10.19401/j.cnki.1007-3639.2025.01.004.
Qianqian GENG, Aimin YANG. Progress and prospect on treatment for radioiodine-refractory thyroid cancer[J]. China Oncology, 2025, 35(1): 30-39. DOI： 10.19401/j.cnki.1007-3639.2025.01.004.
摘要
大多数分化型甲状腺癌患者能够从手术、放射性碘-131和促甲状腺激素（thyroid-stimulating hormone，TSH）抑制治疗中获益，预后良好。一旦发展为碘难治性甲状腺癌，则预后较差且治疗手段有限、治疗效果局限，是近年来的研究热点。随着对肿瘤发生、发展机制的深入研究以及各种诊疗技术的快速发展，新药物和新疗法在碘难治性甲状腺癌领域均有显著进展。新型靶向药物的研发，为碘难治性甲状腺癌治疗带来了革命性的突破。其中以索拉非尼和仑伐替尼为代表的多靶点酪氨酸激酶抑制剂（multi-target tyrosine kinase inhibitor，mTKI）能够显著延长患者的无进展生存期，开启了碘难治性甲状腺癌靶向治疗的新时代。卡博替尼作为TKI治疗失败后的二线治疗也取得了令人瞩目的疗效。国产TKI药物如阿帕替尼和安罗替尼在碘难治性甲状腺癌靶向治疗中的疗效和安全性方面表现俱佳，备受关注。此外靶向
BRAF
V600E突变、
RET
融合及
NTRK
融合基因的特异性靶点酪氨酸激酶抑制剂（达拉非尼、普拉替尼/塞普替尼、拉罗替尼）使得碘难治性分化型甲状腺癌跨进了精准治疗时代。对于存在
RET
融合/
NTRK
融合者，指南推荐首先选择特异性靶点酪氨酸激酶抑制剂，优于泛靶点激酶抑制剂；若无上述基因突变者，泛靶点激酶抑制剂（索拉非尼和仑伐替尼）是标准的一线治疗选择。MEK抑制剂（司美替尼）辅助诱导再分化有望恢复碘难治性甲状腺癌患者的部分摄碘功能，在此基础上的靶碘联合治疗未来也将是一个非常有前途的策略。而免疫检查点抑制剂单药治疗碘难治性甲状腺癌的结果并不乐观，但其与TKI的联合应用则显示出一定的安全性和有效性，值得期待。由于耐药以及无法耐受的不良反应等原因，积极探索新疗法是十分必要的。核医学分子影像指导下的放射性核素治疗或将为碘难治性甲状腺癌患者带来新的希望。靶向前列腺特异性膜抗原（prostate-specific membrane antigen，PSMA）、生长抑素受体（somatostatin receptor，SSTR）及成纤维细胞激活蛋白抑制剂（fibroblast-activating protein inhibitor，FAPi）等放射性配体/受体治疗具有靶向性、可视化及诊疗一体化等特点，并在碘难治性甲状腺癌中进行了初步尝试，证实其在TKI治疗后疾病进展患者中具有较好的可行性。本文就近几年在碘难治性分化型甲状腺癌治疗领域的新药物和新技术进行综述，辅助指导临床的同时，期盼未来能拥有更多个体化、精准化的治疗选择，来进一步提升这部分患者的生存质量和生存期。
Abstract
Most patients with differentiated thyroid cancer benefit from surgery
radioactive iodine-131 therapy and TSH suppression therapy
resulting in a favorable prognosis. However
once radioactive iodine refractory thyroid cancer (RAIR-DTC) develops
the prognosis becomes significantly poorer
treatment options are limited
and therapeutic efficacy is constrained. This has emerged as a research focus in recent years. With advancements in understanding tumor mechanisms and rapid developments in diagnostic and therapeutic technologies
significant progress has been made in new drugs and new treatments for RAIR-DTC. The development of novel targeted therapies ha
s revolutionized the management. Notably
multi-target tyrosine kinase inhibitor (mTKI) such as sorafenib and lenvatinib has demonstrated significant improvements in progression-free survival
thereby establishing targeted therapy as a viable option for RAIR-DTC. Cabozantinib has also shown promising results as a second-line treatment following TKI failure. Other TKIs like apatinib and anlotinib have also arnered attention due to efficacy and safety. Additionally
specific TKI targeting
BRAF
V600E mutations
RET
fusions and
NTRK
fusion genes have ushered in an era of precision medicine for RAIR-DTC. Thus
for patients with
RET
or
NTRK
fusions
guidelines recommend prioritizing specific target TKI over pan-target kinase inhibitors. If no such gene mutations are present
pan-target kinase inhibitors are considered as the standard first-line treatments. MEK inhibitors (selumetinib) may induce redifferentiation
potentially restoring iodine uptake. Consequently
the combination of targeted therapy and iodine-131 therapy represents a promising strategy. While immune checkpoint inhibitors only have not yielded optimistic results in RAIR-DTC
combination with TKIs has shown certain safety and efficacy
warranting further exploration. However
given issues of drug resistance and intolerable side effects
it is imperative to explore new treatments. Radionuclide therapy guided by nuclear medicine molecular imaging offers potential hope for RAIR-DTC patients. Targeted radioligand/receptor therapies
such as PSMA
SSTR and FAPi
exhibit characteristics of targeting
visualization and integration of diagnosis and treatment. Initial trials of them in RAIR-DTC patients with TKIs treatment failure have been confirmed feasibility. This review summarized recent advances in new drugs and new technologies for RAIR-DTC treatment
aiming to guide clinical practice and anticipate more personalized and precise treatment options to improve quality of lif
e and survival.
关键词
Keywords
references
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