放射性碘难治性甲状腺癌的临床试验现状及未来展望  

Current status and future prospects of clinical trials for radioiodine-refractory thyroid cancer

作　　者：李汝平 杨辉 LI Ruping;YANG Hui(Department of Nuclear Medicine,The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer Hospital,Zhengzhou 450008,Henan Province,China;Key Laboratory of Precision Diagnosis and Treatment in Oncology Nuclear Medicine for Henan Provincial,Zhengzhou 450003,Henan Province,China)

机构地区：[1]郑州大学附属肿瘤医院(河南省肿瘤医院)核医学科,河南郑州450008 [2]河南省肿瘤核医学精准诊疗医学重点实验室,河南郑州450003

出　　处：《中国癌症杂志》2025年第1期40-48,共9页China Oncology

基　　金：河南省科技攻关项目(242102311045);国家自然科学基金(82402330);河南省卫生健康委员会科技攻关项目(LHGJ20240132)。

摘　　要：放射性碘难治性甲状腺癌(radioiodine-refractory thyroid cancer,RAIRTC)是指无法或很难从^(131)I治疗中获益的甲状腺癌,目前常涉及的RAIR-TC主要是原本分化较好的分化型甲状腺癌(differentiated thyroid cancer,DTC),随着病程或^(131)I治疗后逐渐出现不摄取^(131)I现象。与能够摄取^(131)I的DTC相比,RAIR-TC的恶性程度明显增加,疾病进展较快,死亡风险较高。因此,RAIRTC的后续治疗已成为国际甲状腺癌研究领域的热点和难点。RAIR-TC的治疗发展经历了多个阶段,从最初的放射性碘治疗到近年来靶向药物的引入,再到免疫治疗的尝试,治疗手段逐步多样化。分子靶向治疗,特别是酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI),为RAIR-TC患者提供了新的治疗选择,但单一靶向治疗的耐药性迅速显现,成为治疗的瓶颈。磷脂酰肌醇3-激酶(phosphoinositide3-kinase,PI3K)/蛋白激酶B(protein kinase,AKT)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)通路和表皮生长因子受体(epidermal growth factor receptor,EGFR)通路的激活是肿瘤逃逸靶向治疗的主要途径。因此,联合治疗策略应运而生,通过靶向多个信号转导通路、优化联合药物的使用,尝试克服单药耐药性。此外,结合患者的分子生物学特征(如BRAF突变、肿瘤免疫表型等)设计个性化治疗方案,已成为研究的热点。免疫治疗,特别是免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)[如派姆单抗(pembrolizumab)],在程序性死亡蛋白配体-1(programmed death ligand-1,PD-L1)高表达的RAIR-TC患者中取得了一定的临床效果。然而,由于RAIR-TC的免疫原性较低,免疫治疗的总体缓解率仍较低,通常为10%~15%。近年来,靶向治疗与免疫治疗的联合治疗策略,如BRAF抑制剂、血管内皮生长因子受体(vascular endothelial growth factor receptor,VEGFR)抑制剂联合程序性死亡蛋白-1(programmed death-1,PD-1)抑制剂的三联疗法,在部分患�Radioiodine-refractory thyroid cancer(RAIR-TC)refers to thyroid cancer that is unable to or difficult to benefit from ^(131)I treatment.The type of RAIR-TC we commonly encounter is differentiated thyroid cancer(DTC),which is originally welldifferentiated but gradually loses its ability to take up iodine during disease progression or after ^(131)I treatment.Compared to DTC that can still take up ^(131)I,RAIR-TC is more malignant,progresses more rapidly,and carries a higher risk of death.Therefore,the subsequent treatment of RAIR-TC has become a hotspot and a challenge in the field of international thyroid cancer research.The treatment of RAIR-TC has evolved through several stages,from initial radioactive iodine therapy to the introduction of targeted drugs in recent years,followed by attempts at immunotherapy,diversifying treatment options.Molecular targeted therapy,especially tyrosine kinase inhibitors(TKIs),has provided new treatment choices for RAIR-TC patients.However,resistance to singleagent targeted therapy has quickly emerged as a bottleneck in treatment efficacy.Studies have shown that the activation of the phosphoinositide3-kinase(PI3K)/protein kinase(AKT)/mammalian target of rapamycin(mTOR)pathway and epidermal growth factor receptor(EGFR)pathway is the main mechanism by which tumors evade targeted therapy.As a result,combination therapy strategies have emerged,aiming to target multiple signaling pathways and optimize the use of combined drugs to overcome singledrug resistance.Additionally,designing personalized treatment plans based on patients’molecular features(such as BRAF mutations and tumor immune phenotypes)has become a research focus.Immunotherapy,especially immune checkpoint inhibitors(ICIs)such as pembrolizumab,has shown some clinical effect in RAIR-TC patients with high level of programmed death ligand-1(PD-L1)expression.However,due to the low immunogenicity of RAIR-TC,the overall response rate to immunotherapy remains relatively low,typically ranging from 10%to 15%.In recent years,combinat

关 键 词：放射性碘难治性甲状腺癌 精准医学 分子靶向治疗 免疫治疗 内照射治疗 

分 类 号：R736.1[医药卫生—肿瘤]