肾细胞癌中的VHL基因突变：作为疾病预后和药物疗效生物标志物的作用。
VHL gene mutations in renal cell carcinoma: role as a biomarker of disease outcome and drug efficacy.
作者信息
Cowey C Lance, Rathmell W Kimryn
机构信息
Lineberger Cancer Center, 450 West Drive, CB 7295, Chapel Hill, NC 27599, USA.
出版信息
Curr Oncol Rep. 2009 Mar;11(2):94-101. doi: 10.1007/s11912-009-0015-5.
Abstract
The therapeutic landscape for renal cell carcinoma (RCC) has changed drastically over the past several years with the emergence of molecularly targeted therapies. With previous prognostic and predictive tools based on studies of patients treated with cytokine therapies, confirmation of these prior methods and discovery of new markers in this new era of targeted therapy are of great importance. Alteration of the von Hippel-Lindau gene (VHL) by mutation, loss of heterozygosity, and promoter methylation has been found to be important to RCC pathogenesis. In this review, we discuss the potential role of VHL mutation as a prognostic and predictive marker for RCC.
摘要
在过去几年中，随着分子靶向治疗的出现，肾细胞癌（RCC）的治疗格局发生了巨大变化。鉴于先前基于细胞因子治疗患者研究的预后和预测工具，在这个靶向治疗的新时代，确认这些先前的方法并发现新的标志物至关重要。已发现通过突变、杂合性缺失和启动子甲基化改变冯·希佩尔-林道基因（VHL）对RCC发病机制很重要。在本综述中，我们讨论了VHL突变作为RCC预后和预测标志物的潜在作用。
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本文引用的文献
1
Using Molecular Biology to Develop Drugs for Renal Cell Carcinoma.利用分子生物学开发治疗肾细胞癌的药物。
Expert Opin Drug Discov. 2008 Mar;3(3):311-327. doi: 10.1517/17460441.3.3.311.
2
Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors.透明细胞肾肿瘤中冯·希佩尔-林道基因改变的识别得到改善。
Clin Cancer Res. 2008 Aug 1;14(15):4726-34. doi: 10.1158/1078-0432.CCR-07-4921.
3
Sorafenib in advanced hepatocellular carcinoma.索拉非尼用于晚期肝细胞癌
N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.
4
von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma.希佩尔-林道基因状态与转移性透明细胞肾细胞癌对血管内皮生长因子靶向治疗的反应
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5
Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma.低碳酸酐酶IX（CAIX）表达及VHL基因突变缺失与透明细胞肾细胞癌的肿瘤侵袭性及不良预后相关。
Int J Cancer. 2008 Jul 15;123(2):395-400. doi: 10.1002/ijc.23496.
6
Cancer statistics, 2008.2008年癌症统计数据。
CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.
7
Genetic and epigenetic alterations in the von hippel-lindau gene: the influence on renal cancer prognosis.冯·希佩尔-林道基因的遗传和表观遗传改变：对肾癌预后的影响。
Clin Cancer Res. 2008 Feb 1;14(3):782-7. doi: 10.1158/1078-0432.CCR-07-1753.
8
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9
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10
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