利用癌症小鼠模型揭示遗传背景依赖性的宇宙。
Deciphering the universe of genetic context-dependencies using mouse models of cancer.
机构信息
Division of Translational Cancer Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany; Institute of Translational Cancer Research and Experimental Cancer Therapy, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany; Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany.
出版信息
Curr Opin Genet Dev. 2019 Feb;54:97-104. doi: 10.1016/j.gde.2019.04.002. Epub 2019 May 9.
Molecular profiling of cancer patients and modelling of human cancer in mice revealed cell type and tissue-specific differences in tumor development and evolution. However, the context-dependent determinants of cancer remain poorly understood. A systematic characterization of the biological underpinnings of context-specificity will, therefore, be pivotal to design more effective therapies. In this review article, we focus on recent advances on molecular, cellular and microenvironmental aspects of context-dependency. We highlight new strategies to study this phenomenon in tumorigenesis and tumor evolution. Notably, we elucidate tissue and cell type-specific signaling cues as well as tumor microenvironment niches, using novel next-generation dual and triple recombinase-based mouse models of cancer.
对癌症患者的分子谱分析以及在小鼠中建立人类癌症模型揭示了肿瘤发生和演化中细胞类型和组织特异性的差异。然而，癌症的上下文相关决定因素仍知之甚少。对上下文特异性的生物学基础进行系统描述，因此对于设计更有效的治疗方法至关重要。在这篇综述文章中，我们重点介绍了上下文相关性的分子、细胞和微环境方面的最新进展。我们强调了在肿瘤发生和肿瘤演化中研究这一现象的新策略。值得注意的是，我们使用新型的基于双和三重重组酶的癌症小鼠模型，阐明了组织和细胞类型特异性的信号通路以及肿瘤微环境小生境。
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