Kou Tadayuki, Kanai Masashi, Matsumoto Shigemi, Okuno Yasushi, Muto Manabu
Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto Department of Clinical Oncology, Kyoto University Hospital Cancer Center, Kyoto.
Department of Clinical System Onco-Informatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Jpn J Clin Oncol. 2016 May;46(5):399-406. doi: 10.1093/jjco/hyw018. Epub 2016 Feb 24.
Comprehensive genomic profiling using next-generation sequencing technologies provides insights into understanding the genomic architecture of human cancer. This new understanding of the cancer genome allows us to identify many more genomic alterations occurring within tumors than before, some of which could be potential therapeutic targets through molecular targeted agents. Currently, a large number of molecular targeted agents are being developed, and consequently, cancer treatment is rapidly shifting from empiric therapy employing cytotoxic anticancer drugs to genotype-directed therapy using molecular targeted agents. In current daily clinical practice, hotspot-based single-gene assays that detect RAS mutations in colorectal cancer or EGFR mutations in non-small cell lung cancer are widely used to identify variants. However, it is becoming evident that more comprehensive genomic analysis is crucial in identifying the patient population that may benefit from molecular targeted therapy and the accelerated development of novel drugs for early clinical trials. For these purposes, an increasing number of gene panel-based targeted sequencing is commercially available in clinical practice from sequencing companies. Despite several challenges in implementing this approach, comprehensive genomic profiling and identification of actionable mutations is likely to become one of the standard options in the management of cancer in the near future. The use of clinical sequencing has the potential to usher a new era in precision medicine for cancer diagnosis and treatment. In this review, we discuss the application of comprehensive genomic profiling using next-generation sequencing technologies in clinical oncology and address the current challenges for its implementation.
使用下一代测序技术进行全面的基因组分析有助于深入了解人类癌症的基因组结构。对癌症基因组的这种新认识使我们能够识别出比以往更多的肿瘤内发生的基因组改变,其中一些可能是通过分子靶向药物的潜在治疗靶点。目前,大量分子靶向药物正在研发中,因此,癌症治疗正在迅速从使用细胞毒性抗癌药物的经验性治疗转向使用分子靶向药物的基因型导向治疗。在当前的日常临床实践中,基于热点的单基因检测用于检测结直肠癌中的RAS突变或非小细胞肺癌中的EGFR突变,被广泛用于识别变异。然而,越来越明显的是,更全面的基因组分析对于确定可能从分子靶向治疗中获益的患者群体以及加速早期临床试验新药的开发至关重要。出于这些目的,越来越多基于基因panel的靶向测序在临床实践中可从测序公司商业获得。尽管实施这种方法存在一些挑战,但全面的基因组分析和可操作突变的识别在不久的将来可能会成为癌症管理的标准选择之一。临床测序的应用有可能开创癌症诊断和治疗精准医学的新时代。在这篇综述中,我们讨论了使用下一代测序技术进行全面基因组分析在临床肿瘤学中的应用,并阐述了其实施目前面临的挑战。