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靶向Brachyury(一种与肿瘤上皮-间质转化相关的转录因子)的癌症疫苗的研发

Development of Cancer Vaccines Targeting Brachyury, a Transcription Factor Associated with Tumor Epithelial-Mesenchymal Transition.

作者信息

Hamilton Duane H, David Justin M, Dominguez Charli, Palena Claudia

机构信息

Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

出版信息

Cells Tissues Organs. 2017;203(2):128-138. doi: 10.1159/000446495. Epub 2017 Feb 20.

DOI:10.1159/000446495
PMID:28214895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5381518/
Abstract

Epithelial-mesenchymal transition (EMT) is recognized as a relevant process during the progression of carcinomas towards metastatic disease. Epithelial cancer cells undergoing an EMT program may acquire mesenchymal features, motility, invasiveness, and resistance to a variety of anticancer therapeutics. Preventing or reverting the EMT process in carcinomas has the potential to minimize tumor dissemination and the emergence of therapeutic resistance. One of the strategies currently under investigation to target tumor cells undergoing EMT is the generation of a sustained immune response directed against an essential molecular driver of the process. This review focuses on the current development of immune-mediated anticancer interventions aimed at targeting a transcription factor, brachyury, associated with human tumor EMT. Also presented here is a summary of recent studies demonstrating a role for EMT in tumor resistance to immune effector cytotoxicity, and the study of novel strategies aimed at reverting the EMT to be used in combination with immune-mediated anticancer interventions.

摘要

上皮-间质转化(EMT)被认为是癌症向转移性疾病进展过程中的一个相关过程。经历EMT程序的上皮癌细胞可能获得间质特征、运动性、侵袭性以及对多种抗癌治疗的抗性。在癌症中预防或逆转EMT过程有可能将肿瘤扩散和治疗抗性的出现降至最低。目前正在研究的针对经历EMT的肿瘤细胞的策略之一是产生针对该过程的关键分子驱动因子的持续免疫反应。本综述聚焦于旨在靶向与人类肿瘤EMT相关的转录因子短尾相关蛋白的免疫介导抗癌干预措施的当前进展。本文还总结了最近的研究,这些研究证明了EMT在肿瘤对免疫效应细胞毒性的抗性中的作用,以及旨在逆转EMT以与免疫介导的抗癌干预措施联合使用的新策略的研究。

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N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.
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The potential role of Brachyury in inducing epithelial-to-mesenchymal transition (EMT) and HIF-1α expression in breast cancer cells.Brachyury在诱导乳腺癌细胞上皮-间质转化(EMT)和缺氧诱导因子-1α(HIF-1α)表达中的潜在作用。
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The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic.
敲低Brachyury通过靶向E2F3抑制乳腺癌细胞增殖和迁移。
J Oncol. 2022 Nov 22;2022:7913067. doi: 10.1155/2022/7913067. eCollection 2022.
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Gene Expression Profiling Identifies Two Chordoma Subtypes Associated with Distinct Molecular Mechanisms and Clinical Outcomes.基因表达谱分析鉴定出两种与不同分子机制和临床结局相关的脊索瘤亚型。
Clin Cancer Res. 2023 Jan 4;29(1):261-270. doi: 10.1158/1078-0432.CCR-22-1865.
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