Pazopanib Efficacy in Renal Cell Carcinoma: Evidence for Predictive Genetic Markers in Angiogenesis-Related and Exposure-Related Genes
Pazopanib Efficacy in Renal Cell Carcinoma: Evidence for Predictive Genetic Markers in Angiogenesis-Related and Exposure-Related Genes
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DOI：
10.1200/jco.2010.32.9110
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发表时间：
2011-06-20
影响因子：
45.3
通讯作者：
Pandite, Lini N.
中科院分区：
文献类型：
--
作者：
Xu, Chun-Fang;Bing, Nan X.;Pandite, Lini N.
帕唑帕尼是一种口服血管生成抑制剂，已被批准用于治疗晚期肾细胞癌（RCC）。对帕唑帕尼单药治疗的反应因患者而异，并且尚未鉴定出预测治疗结果的有效生物标志物。我们测试的假设，这种变异性是部分依赖于生殖系的遗传变异，可能会影响帕唑帕尼曝光或血管生成pathways.Patients and MethodsTwenty七个功能多态性内13个基因进行了评估，在397例肾细胞癌患者。分别使用考克斯比例风险模型和比例优势模型分析与无进展生存期（PFS）和客观缓解率（RR）的遗传相关性。结果IL 8和HIF 1A的三种多态性以及HIF 1A、NR 1 I 2和VEGFA的五种多态性表现出名义上显着的相关性（P
PurposePazopanib, an oral angiogenesis inhibitor, is approved for the treatment of advanced renal cell carcinoma (RCC). Response to pazopanib monotherapy varies between patients, and no validated biomarkers predictive of treatment outcome have been identified. We tested the hypothesis that this variability is partially dependent on germline genetic variants that may affect pazopanib exposure or angiogenesis pathways.Patients and MethodsTwenty-seven functional polymorphisms within 13 genes were evaluated in 397 patients with RCC. Genetic association with progression-free survival (PFS) and objective response rate (RR) was analyzed using the Cox proportional hazards model and proportional odds model, respectively.ResultsThree polymorphisms in IL8 and HIF1A and five polymorphisms in HIF1A, NR1I2, and VEGFA showed nominally significant association (P