Department of Molecular and Human Genetics, Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Nat Rev Clin Oncol. 2019 Apr;16(4):256-268. doi: 10.1038/s41571-018-0135-7.
Cancer genomics research aims to advance personalized oncology by finding and targeting specific genetic alterations associated with cancers. In genome-driven oncology, treatments are selected for individual patients on the basis of the findings of tumour genome sequencing. This personalized approach has prolonged the survival of subsets of patients with cancer. However, many patients do not respond to the predicted therapies based on the genomic profiles of their tumours. Furthermore, studies pairing genomic and proteomic analyses of samples from the same tumours have shown that the proteome contains novel information that cannot be discerned through genomic analysis alone. This observation has led to the concept of proteogenomics, in which both types of data are leveraged for a more complete view of tumour biology that might enable patients to be more successfully matched to effective treatments than they would using genomics alone. In this Perspective, we discuss the added value of proteogenomics over the current genome-driven approach to the clinical characterization of cancers and summarize current efforts to incorporate targeted proteomic measurements based on selected/multiple reaction monitoring (SRM/MRM) mass spectrometry into the clinical laboratory to facilitate clinical proteogenomics.
癌症基因组学研究旨在通过寻找和靶向与癌症相关的特定遗传改变来推进肿瘤个体化治疗。在基于基因组的肿瘤学中，根据肿瘤基因组测序的结果为个体患者选择治疗方法。这种个体化方法延长了部分癌症患者的生存期。然而，许多患者对基于肿瘤基因组图谱预测的治疗方法没有反应。此外，对来自同一肿瘤的基因组和蛋白质组分析样本进行的研究表明，蛋白质组包含通过单独的基因组分析无法识别的新信息。这一观察结果催生了蛋白质基因组学的概念，即利用这两种类型的数据来更全面地了解肿瘤生物学，这可能使患者比仅使用基因组学更成功地匹配到有效治疗方法。在本观点文章中，我们讨论了蛋白质基因组学相对于当前基于基因组的癌症临床特征分析方法的附加价值，并总结了当前将基于选择/多重反应监测（SRM/MRM）质谱的靶向蛋白质组测量纳入临床实验室以促进临床蛋白质基因组学的努力。
