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首页> 外文期刊>Pharmacogenetics and genomics >Application of T cell-based transcriptomics to identify three candidate biomarkers for monitoring anti-TGFbetaR therapy.
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Application of T cell-based transcriptomics to identify three candidate biomarkers for monitoring anti-TGFbetaR therapy.

机译：基于T细胞的转录组学在确定三种候选生物标志物以监测抗TGFbetaR治疗中的应用。

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OBJECTIVES: The development of targeted drugs would greatly benefit from the simultaneous identification of biomarkers to determine the aspects of bioactivity, drug safety and efficacy, particularly when affecting receptor-signaling pathways. However, the establishment of appropriate systems to monitor drug-induced events requires an accessible surrogate tissue for functional read out. METHODS: Therefore we present a universal platform based upon T cell-based gene expression profiling for the identification of biomarkers using the antitransforming growth factor beta receptor inhibitor LY2109761 as an example. RESULTS: Our initial screen revealed 12 candidate genes specifically regulated in T cells by the inhibitor. In subsequent in-vitro and in-vivo analyses, the combined monitoring of independent gene regulation of three genes was established in peripheral blood mononuclear cells as novel pharmacodynamic candidate biomarkers for antitransforming growth factor beta receptor based therapies. CONCLUSION: Overall, the proposed concept of biomarker identification can be easily adapted towards other drug candidates for whom gene regulation can be established in cellular components of peripheral blood.
机译：目标：靶向药物的开发将受益于同时鉴定生物标志物以确定生物活性，药物安全性和有效性的方面，特别是在影响受体信号通路时。然而，建立适当的系统来监测药物诱发的事件需要功能性读出的可替代组织。方法：因此，我们提出了一个基于T细胞的基因表达谱为基础的通用平台，以使用抗转化生长因子β受体抑制剂LY2109761为例来鉴定生物标志物。结果：我们的初步筛选揭示了该抑制剂在T细胞中特异性调控的12个候选基因。在随后的体外和体内分析中，在外周血单核细胞中建立了对三个基因的独立基因调节的联合监测，作为基于抗转化生长因子β受体疗法的新型药效候选生物标志物。结论：总的来说，所提出的生物标志物鉴定概念可以很容易地适应于其他候选药物，在外周血细胞成分中可以建立基因调控的候选药物。

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