Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
Nat Rev Nephrol. 2020 Aug;16(8):435-451. doi: 10.1038/s41581-020-0301-x. Epub 2020 Jun 19.
The treatment landscape of metastatic renal cell carcinoma (RCC) has been revolutionized over the past two decades, bringing forth an era in which more than a dozen therapeutic agents are now available to treat patients. As a consequence, personalized care has become a critical part of developing effective treatment guidelines and improving patient outcomes. One of the most important emerging aspects of precision medicine in cancer is matching patients and treatments based on the genomic characteristics of an individual and their tumour. Despite the lack of a single genomic predictor of treatment response or prognostication feature in RCC, emerging research suggests that the identification of such markers remains promising. Mutations in VHL and alterations in its downstream pathways are the mainstay of RCC development and progression. However, the predictive value of VHL mutations has been questioned. Further research has examined mutations in genes involved in chromosome remodelling (for example, PBRM1, BAP1 and SETD2), DNA methylation and DNA damage repair, all of which have been associated with clinical outcomes. Here, we provide a comprehensive overview of genomic evidence in the context of RCC and its potential predictive and prognostic value.
在过去的二十年中，转移性肾细胞癌（RCC）的治疗格局发生了革命性的变化，现在有十几种治疗药物可用于治疗患者。因此，个性化护理已成为制定有效治疗指南和改善患者预后的关键部分。癌症精准医学中最引人注目的新兴方面之一是根据个体及其肿瘤的基因组特征来匹配患者和治疗方法。尽管 RCC 中缺乏单一的基因组预测治疗反应或预后特征的预测因子，但新兴研究表明，识别此类标志物仍然具有很大的潜力。VHL 突变及其下游途径的改变是 RCC 发生和进展的主要因素。然而，VHL 突变的预测价值一直受到质疑。进一步的研究检查了涉及染色体重塑（例如，PBRM1、BAP1 和 SETD2）、DNA 甲基化和 DNA 损伤修复的基因中的突变，所有这些都与临床结果相关。在这里，我们全面概述了 RCC 及其潜在预测和预后价值的基因组证据。
