Ocak S, Sos M L, Thomas R K, Massion P P
Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232-6838, USA.
Eur Respir J. 2009 Aug;34(2):489-506. doi: 10.1183/09031936.00042409.
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.
在过去十年中,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应用于加深我们对这种异质性疾病分子发病机制的理解,并制定旨在改善肺癌患者管理的策略。最终,这些方法应能带来用于早期诊断的灵敏、特异且非侵入性的方法,并有助于预测治疗反应和预后,以及识别潜在的新型治疗靶点。基因组研究率先推动了该领域的发展,它为肺癌分子生物学提供了新的见解,并产生了疾病进展的候选生物标志物。肺癌发生由导致异常基因功能的遗传和表观遗传改变驱动;然而,挑战仍然是确定关键的调控机制,并区分驱动性改变和对癌症发展可能有微小但累加效应的乘客性改变。DNA甲基化和组蛋白修饰介导的表观遗传调控调节染色质结构,进而激活或沉默基因表达。蛋白质组学方法对这些分子研究起到了至关重要的补充作用,因为癌细胞的表型由蛋白质决定,不能仅通过基因组学或转录组学来预测。本文重点介绍现有的技术平台以及一些提议的临床应用。我们在此阐述了“组学”如何彻底改变了我们研究肺癌生物学的方法,并有望实现肺癌的个性化管理。