I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Omicsway Corp., Walnut, CA, USA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Omicsway Corp., Walnut, CA, USA; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
Semin Cancer Biol. 2020 Feb;60:311-323. doi: 10.1016/j.semcancer.2019.07.010. Epub 2019 Aug 11.
Molecular diagnostics is becoming one of the major drivers of personalized oncology. With hundreds of different approved anticancer drugs and regimens of their administration, selecting the proper treatment for a patient is at least nontrivial task. This is especially sound for the cases of recurrent and metastatic cancers where the standard lines of therapy failed. Recent trials demonstrated that mutation assays have a strong limitation in personalized selection of therapeutics, consequently, most of the drugs cannot be ranked and only a small percentage of patients can benefit from the screening. Other approaches are, therefore, needed to address a problem of finding proper targeted therapies. The analysis of RNA expression (transcriptomic) profiles presents a reasonable solution because transcriptomics stands a few steps closer to tumor phenotype than the genome analysis. Several recent studies pioneered using transcriptomics for practical oncology and showed truly encouraging clinical results. The possibility of directly measuring of expression levels of molecular drugs' targets and profiling activation of the relevant molecular pathways enables personalized prioritizing for all types of molecular-targeted therapies. RNA sequencing is the most robust tool for the high throughput quantitative transcriptomics. Its use, potentials, and limitations for the clinical oncology will be reviewed here along with the technical aspects such as optimal types of biosamples, RNA sequencing profile normalization, quality controls and several levels of data analysis.
分子诊断正成为个性化肿瘤学的主要驱动力之一。有数百种不同的批准用于治疗癌症的药物和方案,为患者选择合适的治疗方法至少不是一件微不足道的任务。对于复发和转移性癌症来说,这一点尤为明显,因为这些癌症的标准治疗方案已经失败。最近的试验表明,突变检测在个性化治疗选择方面有很大的局限性,因此,大多数药物无法进行排序,只有一小部分患者可以从筛选中受益。因此,需要其他方法来解决寻找合适的靶向治疗方法的问题。分析 RNA 表达(转录组)谱是一个合理的解决方案,因为转录组比基因组分析更接近肿瘤表型。最近的几项研究率先将转录组学用于实际的肿瘤学,并取得了非常令人鼓舞的临床结果。直接测量分子药物靶点的表达水平和分析相关分子通路的激活情况的可能性,使得所有类型的分子靶向治疗都可以进行个性化优先排序。RNA 测序是高通量定量转录组学最强大的工具。本文将回顾 RNA 测序在临床肿瘤学中的应用、潜力和局限性,以及技术方面的问题,如最佳生物样本类型、RNA 测序谱标准化、质量控制和数据分析的几个层次。