Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance

IF 15.8 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Huize Shen , Rui Zhu , Yanyang Liu , Yangjian Hong , Jiaming Ge , Jie Xuan , Wenyuan Niu , Xuefei Yu , Jiang-Jiang Qin , Qinglin Li
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Abstract

Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.

Abstract Image

放射性碘难治性甲状腺癌症:放射性碘耐药性的分子机制和治疗策略
放射性碘难治性分化型癌症(RAIR-DTC)很难用放射性碘治疗,因为在甲状腺毛囊细胞的基底膜中缺乏用于碘摄取的碘化钠转运蛋白(NIS)。这通常是由于基因的突变或重排以及信号通路的异常激活,导致甲状腺特异性基因的异常表达,导致分化的甲状腺癌症细胞对放射性碘治疗产生耐药性。因此,用多激酶抑制剂(MKIs)等化学物质抑制RAIR-DTC的增殖和生长,恢复其分化,进而进行放射性碘治疗已成为一线治疗策略和主要研究方向。调节这些激酶或信号通路的药物已经在临床和临床前环境中进行了研究。在这篇综述文章中,我们总结了导致RAIR-DTC放射性碘耐药性的主要基因突变、基因重排和信号通路的异常表达,以及已在临床和临床前试验中测试的药物。
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来源期刊
Drug Resistance Updates
Drug Resistance Updates 医学-药学
CiteScore
26.20
自引率
11.90%
发文量
32
审稿时长
29 days
期刊介绍: Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation. Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective. *Expert reviews in clinical and basic drug resistance research in oncology and infectious disease *Describes emerging technologies and therapies, particularly those that overcome drug resistance *Emphasises common themes in microbial and cancer research
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