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浙江大学学报(医学版)  2021, Vol. 50 Issue (6): 685-693    DOI: 10.3724/zdxbyxb-2021-0249
专题报道     
甲状腺未分化癌靶向治疗研究进展
钱晨宏1,2,蒋烈浩2,3,许世莹2,4,王佳峰2,3,谭卓2,3,忻莹2,3,葛明华1,2,3,*()
1.蚌埠医学院研究生院,安徽 蚌埠 233030
2.杭州医学院附属人民医院 浙江省人民医院耳鼻咽喉-头颈外科中心头颈外科, 浙江 杭州 310014
3.浙江省内分泌腺体疾病诊治研究重点实验室,浙江 杭州 310014
4.浙江中医药大学第二临床医学院,浙江 杭州 310053
Advances in targeted therapy for anaplastic thyroid carcinoma
QIAN Chenhong1,2,JIANG Liehao2,3,XU Shiying2,4,WANG Jiafeng2,3,TAN Zhuo2,3,XIN Ying2,3,GE Minghua1,2,3,*()
1. Graduate School, Bengbu Medical College, Bengbu 233030, Anhui Province, China;
2. Department of Head and Neck Surgery, Center of Otolaryngology, Head and Neck Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China;
3. Zhejiang Provincial Key Laboratory of Endocrine Gland Diseases, Hangzhou 310014, China;
4. The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
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摘要:

甲状腺未分化癌(ATC)是一种恶性程度高、侵袭性强的甲状腺恶性肿瘤,发病迅速,预后差,目前尚缺乏有效治疗手段。分子靶向治疗为ATC治疗提供了一种新思路。酪氨酸激酶抑制剂乐伐替尼在治疗ATC患者临床试验中疗效良好;鼠类肉瘤病毒癌基因同源物B1(BRAF)基因抑制剂达拉非尼联合曲美替尼治疗BRAFV600E阳性ATC患者的有效性已在临床试验中得到证实,2021年美国国家综合癌症网络甲状腺癌临床实践指南中提出达拉非尼联合曲美替尼可作为治疗BRAFV600E阳性ATC患者治疗的首选方式;免疫检查点抑制剂帕博利珠单抗应用于高肿瘤突变负荷甲状腺癌治疗,可作为程序性死亡蛋白1高表达ATC患者的首选方式;哺乳动物雷帕霉素靶蛋白通路抑制剂、过氧化物酶体增殖物激活受体γ激动剂、靶向内皮生长因子受体的单克隆抗体西妥昔单抗及新型血管阻断剂康布瑞汀磷酸二钠仍处于临床研究阶段。本文综述了目前ATC靶向药物治疗的研究进展。

关键词: 甲状腺未分化癌靶向治疗免疫治疗临床治疗综述    
Abstract:

Anaplastic thyroid carcinoma (ATC) is a highly malignant and aggressive thyroid malignancy with rapid onset and poor prognosis. There is no effective treatment for ATC yet. Molecular targeted therapy provides a new idea for ATC treatment. Tyrosine kinase inhibitor lenvatinib has potential in treating ATC patients with favorable efficacy in clinical trials. The effectiveness of the v-raf murine sarcoma viral oncogene homologue B1 (BRAF) gene inhibitor dabrafenib in combination with trametinib for the treatment of BRAFV600E positive ATC patients has been demonstrated in clinical trials. The NCCN clinical practice guidelines in oncology has proposed dabrafenib in combination with trametinib as the preferred modality for the treatment of patients with BRAFV600E positive ATC. The immune checkpoint inhibitor pembrolizumab can be applied to treat thyroid cancer with high tumor mutational load and may be considered as the preferred modality for the treatment of ATC patients with high programmed death ligand-1 expression. The mammalian target of rapamycin pathway inhibitors, peroxisome proliferators-activated receptor γ agonists, endothelial growth factor receptors-targeting monoclonal antibody cetuximab and novel vascular blocker fosbretabulin are still in the clinical research stage, which are expected to provide new directions for the development of novel targeted drugs. This article reviews the current research progress on targeted drugs for the treatment of ATC.

Key words: Anaplastic thyroid carcinoma    Targeted therapy    Immunotherapy    Clinical treatment    Review
收稿日期: 2021-08-25 出版日期: 2022-03-22
CLC:  R736.1  
基金资助: 国家自然科学基金(81872170);区域创新发展联合基金(U20A20382);浙江省医学会临床科研基金(2017ZYC-A03)
通讯作者: 葛明华     E-mail: geminghua@hmc.edu.cn
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引用本文:

钱晨宏,蒋烈浩,许世莹,王佳峰,谭卓,忻莹,葛明华. 甲状腺未分化癌靶向治疗研究进展[J]. 浙江大学学报(医学版), 2021, 50(6): 685-693.

QIAN Chenhong,JIANG Liehao,XU Shiying,WANG Jiafeng,TAN Zhuo,XIN Ying,GE Minghua. Advances in targeted therapy for anaplastic thyroid carcinoma. J Zhejiang Univ (Med Sci), 2021, 50(6): 685-693.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0249        https://www.zjujournals.com/med/CN/Y2021/V50/I6/685

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