Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8069, St. Louis, Missouri 63110, USA.
Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.
Nat Rev Dis Primers. 2017 Mar 9;3:17009. doi: 10.1038/nrdp.2017.9.
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery, whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in the treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitinib, which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGFR), and everolimus and temsirolimus, which inhibit mechanistic target of rapamycin complex 1 (mTORC1), being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies, such as nivolumab, have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the biology of RCC, with a focus on ccRCC, as well as updates to complement the current clinical guidelines and an outline of potential future directions for RCC research and therapy.
肾细胞癌（RCC）表示起源于肾上皮的癌症，占肾脏癌症的>90%。该疾病包括>10 种组织学和分子亚型，其中透明细胞 RCC（ccRCC）最为常见，占大多数癌症相关死亡。虽然已经描述了一段时间的体细胞 VHL 突变，但最近的癌症基因组研究已经确定了表观遗传调节基因的突变，并表明明显的肿瘤内异质性，这可能具有预后、预测和治疗相关性。局部 RCC 可以通过手术成功治疗，而转移性 RCC 对常规化疗具有抗性。然而，在过去十年中，转移性 RCC 的治疗取得了显著进展，靶向药物包括索拉非尼、舒尼替尼、贝伐单抗、帕唑帕尼和阿昔替尼，它们抑制血管内皮生长因子（VEGF）及其受体（VEGFR），以及依维莫司和替西罗莫司，它们抑制雷帕霉素靶蛋白复合物 1（mTORC1），已被批准。自 2015 年以来，已经批准了除 VEGFR 以外还有其他靶点的药物，如卡博替尼和仑伐替尼；免疫疗法，如纳武单抗，也已被添加到转移性 RCC 的治疗方案中。在这里，我们提供了 RCC 生物学的概述，重点是 ccRCC，并更新了补充当前临床指南的内容，并概述了 RCC 研究和治疗的潜在未来方向。
