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Molecular classification of solid tumours: towards pathway-driven therapeutics

机译:实体瘤的分子分类:途径驱动疗法

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The last decade has witnessed unprecedented developments in the genetic and epigenetic analyses of solid tumours. Transcriptional and DNA copy-number studies have improved our understanding and classification of solid tumours and highlighted the patterns of genomic aberrations associated with outcome. The identification of altered transcriptional and translational silencing by microRNAs and epigenetic modification by methylation in tumours has showed a layer of additional intricacy to the regulation of gene expression in different tumour types. The advent of massive parallel sequencing has allowed whole cancer genomes to be sequenced with extraordinary speed and accuracy providing insight into the bewildering complexity of gene mutations present in solid tumours. Functional genomic studies using RNA interference-screening tools promises to improve the classification of solid tumours by probing the relevance of each gene to tumour phenotype. In this review, we discuss how these studies have contributed to solid tumour classification and why such studies are central to the future of oncology. We suggest that these developments are gradually leading to a change in emphasis of early clinical trials to a therapeutic model guided by the molecular classification of tumours. The investigation of drug efficacy later in development is beginning to rely on patient selection defined by predictive molecular criteria that complement solid tumour classification based on anatomic site.
机译:在过去的十年中,实体瘤的遗传和表观遗传学分析取得了空前的发展。转录和DNA拷贝数研究提高了我们对实体瘤的理解和分类,并突出了与预后相关的基因组畸变模式。通过microRNA识别改变的转录和翻译沉默以及通过甲基化在肿瘤中进行表观遗传修饰,这已为不同肿瘤类型的基因表达调控增加了一层复杂性。大规模并行测序的出现使整个癌症基因组得以以非凡的速度和准确性进行测序,从而洞悉了实体瘤中令人困惑的基因突变的复杂性。使用RNA干扰筛查工具的功能基因组研究有望通过探索每种基因与肿瘤表型的相关性来改善实体瘤的分类。在这篇综述中,我们讨论了这些研究如何促进实体瘤的分类以及为什么这些研究对肿瘤学的未来至关重要。我们建议这些发展正在逐步导致早期临床试验重点转向以肿瘤的分子分类为指导的治疗模型。后期对药物功效的研究开始依赖于患者的选择,该患者的选择由预测分子标准定义,该分子标准可补充基于解剖部位的实体肿瘤分类。

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