Institute of Urologic Oncology, UCLA David Geffen School of Medicine, Los Angeles, California 90095-1738, USA.
Oncologist. 2011;16 Suppl 2(Suppl 2):4-13. doi: 10.1634/theoncologist.2011-S2-04.
In the past 15 years, there has been an increased understanding of the tumor biology of renal cell carcinoma (RCC). The identification of vascular endothelial growth factor (VEGF), its related receptor (VEGFR), and the mammalian target of rapamycin as dysregulated signaling pathways in the development and progression of RCC has resulted in the rational development of pharmaceutical agents capable of specifically targeting key steps in these pathways. Clinical trials have demonstrated survival benefit with these agents, particularly in clear cell RCC patients. However, metastatic RCC will progress in all patients, resulting in a critical need to determine patient risk and optimize treatment. The goal of this article is to highlight the significant breakthroughs made in understanding the critical genetic alterations and signaling pathways underlying the pathogenesis of RCC. The discovery of prognostic factors and development of comprehensive nomograms to stratify patient risk and predictive biomarkers to facilitate individualized treatment selection and predict patient response to therapy also are reviewed.
在过去的 15 年中，人们对肾细胞癌（RCC）的肿瘤生物学有了更深入的了解。血管内皮生长因子（VEGF）、其相关受体（VEGFR）和哺乳动物雷帕霉素靶蛋白（mTOR）作为 RCC 发生和进展中失调的信号通路已被确定，这导致了能够特异性靶向这些通路关键步骤的药物的合理开发。临床试验表明，这些药物具有生存获益，特别是在透明细胞 RCC 患者中。然而，转移性 RCC 会在所有患者中进展，因此迫切需要确定患者的风险并优化治疗。本文的目的是强调在理解 RCC 发病机制的关键遗传改变和信号通路方面取得的重大突破。还回顾了预后因素的发现以及综合列线图的开发，以对患者的风险进行分层，并预测生物标志物以促进个体化治疗选择并预测患者对治疗的反应。
