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甲状腺癌的小鼠模型:连接发病机制和新疗法。

Mouse models of thyroid cancer: Bridging pathogenesis and novel therapeutics.

机构信息

Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China.

Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, People's Republic of China; Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China.

出版信息

Cancer Lett. 2020 Jan 28;469:35-53. doi: 10.1016/j.canlet.2019.09.017. Epub 2019 Oct 4.

Abstract

Due to a global increase in the incidence of thyroid cancer, numerous novel mouse models were established to reveal thyroid cancer pathogenesis and test promising therapeutic strategies, necessitating a comprehensive review of translational medicine that covers (i) the role of mouse models in the research of thyroid cancer pathogenesis, and (ii) preclinical testing of potential anti-thyroid cancer therapeutics. The present review article aims to: (i) describe the current approaches for mouse modeling of thyroid cancer, (ii) provide insight into the biology and genetics of thyroid cancers, and (iii) offer guidance on the use of mouse models for testing potential therapeutics in preclinical settings. Based on research with mouse models of thyroid cancer pathogenesis involving the RTK, RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, SRC, and JAK-STAT signaling pathways, inhibitors of VEGFR, MEK, mTOR, SRC, and STAT3 have been developed as anti-thyroid cancer drugs for "bench-to-bedside" translation. In the future, mouse models of thyroid cancer will be designed to be ''humanized" and "patient-like," offering opportunities to: (i) investigate the pathogenesis of thyroid cancer through target screening based on the CRISPR/Cas system, (ii) test drugs based on new mouse models, and (iii) explore the underlying mechanisms based on multi-omics.

摘要

由于全球甲状腺癌发病率的增加,许多新型的小鼠模型被建立起来,以揭示甲状腺癌的发病机制并测试有前途的治疗策略,这就需要对涵盖(i)小鼠模型在甲状腺癌发病机制研究中的作用,以及(ii)潜在抗甲状腺癌治疗药物的临床前测试的转化医学进行全面综述。本文旨在:(i)描述当前用于甲状腺癌小鼠建模的方法,(ii)深入了解甲状腺癌的生物学和遗传学,以及(iii)为在临床前环境中测试潜在治疗药物提供小鼠模型的使用指导。基于涉及 RTK、RAS/RAF/MEK/ERK、PI3K/AKT/mTOR、SRC 和 JAK-STAT 信号通路的甲状腺癌发病机制的小鼠模型研究,已经开发出针对 VEGFR、MEK、mTOR、SRC 和 STAT3 的抑制剂作为用于“从实验室到病床”转化的抗甲状腺癌药物。未来,将设计出“人源化”和“患者样”的甲状腺癌小鼠模型,为:(i)通过基于 CRISPR/Cas 系统的靶向筛选来研究甲状腺癌的发病机制,(ii)基于新型小鼠模型进行药物测试,以及(iii)基于多组学来探索潜在机制提供机会。

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