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High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

机译:肺癌中的高通量分子分析:对生物学和潜在临床应用的见解。

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During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.
机译:在过去的十年中,包括基因组学,表观基因组学,转录组学和蛋白质组学在内的高通量技术已被用于进一步了解这种异质性疾病的分子发病机制,并制定旨在改善肺癌患者管理的策略。最终,这些方法应导致敏感,特异性和非侵入性的早期诊断方法,并有助于预测对治疗和结果的反应,并确定潜在的新型治疗靶标。基因组研究是第一个通过向肺癌分子生物学提供新颖见解并产生疾病进展的候选生物标志物来推动该领域发展的研究。肺癌的致癌作用是由引起异常基因功能的遗传和表观遗传改变引起的。然而,挑战仍然是查明关键的监管控制机制,以及将驾驶员与乘客变更区分开来,这些变更可能对癌症的发展影响很小,但又有累加作用。通过DNA甲基化和组蛋白修饰进行的表观遗传调控可调节染色质结构,进而激活或沉默基因表达。蛋白质组学方法是对这些分子研究的重要补充,因为癌细胞的表型是由蛋白质决定的,而不能仅由基因组学或转录组学来预测。本文重点介绍可用的技术平台和一些建议的临床应用。我们在这里说明“组学”是如何彻底改变了我们的肺癌生物学方法,并有望对肺癌进行个性化管理。

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