Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma.
Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma.
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DOI：
10.1007/s00280-014-2539-0
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发表时间：
2014-10
影响因子：
3
通讯作者：
Williams, J. Andrew
中科院分区：
文献类型：
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作者：
Motzer, Robert J.;Hutson, Thomas E.;Hudes, Gary R.;Figlin, Robert A.;Martini, Jean-Francois;English, Patricia A.;Huang, Xin;Valota, Olga;Williams, J. Andrew
舒尼替尼是一线晚期肾细胞癌 (RCC) 标准治疗药物。在一项比较舒尼替尼治疗方案的随机 II 期试验中，单独的探索性生物标志物分析研究了疗效与选定血清、种系单核苷酸多态性 (SNP) 或肿瘤标志物的相关性。晚期 RCC 患者按照批准的 4 周连用 2 周停药方案接受一线舒尼替尼 50 mg/天（n = 146）或 37.5 mg/天连续给药（n = 146）。进行了以下相关性分析：（1）通过两个不同的多重（n < 1,000）平台，实体瘤定义的肿瘤反应与血清可溶性蛋白水平的反应评估标准； (2) 血管内皮生长因子 (VEGF)-A 和 VEGF 受体 (VEGFR)3 基因中种系 SNP 的反应和事件发生时间结果； (3) 缺氧诱导因子 1-α (HIF-1α) 和碳酸酐酶-IX 的肿瘤免疫组织化学状态或肿瘤 Von Hippel-Lindau (VHL) 基因失活状态的反应和事件发生时间结果。两个平台都确定较低的基线血管生成素-2 (Ang-2) 和较高的基线基质金属蛋白酶-2 (MMP-2) 水平与肿瘤反应具有统计学显着相关性。 VEGF-A 或 VEGFR3 SNP 与结果之间没有显着相关性。肿瘤表达组中 HIF-1α 百分比 0-2（HIF-1α 低）与 3-4（HIF-1α 高；p = 0.034）相比，无进展生存期更长。结果与每种 VHL 失活机制 [突变（86% 的 VHL 失活患者）、甲基化 (14%) 和大缺失 (7%)] 或组合机制之间没有显着相关性。血清 Ang-2 和 MMP-2 以及肿瘤 HIF-1α 被确定为晚期 RCC 中舒尼替尼活性的相关基线生物标志物，值得进一步研究其预后与预测价值。本文的在线版本 (doi:10.1007/s00280-014-2539-0) 包含补充材料，可供授权用户使用。
Sunitinib is a first-line advanced renal cell carcinoma (RCC) standard of care. In a randomized phase II trial comparing sunitinib treatment schedules, separate exploratory biomarker analyses investigated the correlations of efficacy with selected serum, germ line single-nucleotide polymorphism (SNP), or tumor markers. Advanced RCC patients received first-line sunitinib 50 mg/day on the approved 4-week-on-2-week-off schedule (n = 146) or 37.5 mg/day continuous dosing (n = 146). The following correlation analyses were performed: (1) response evaluation criteria in solid tumors-defined tumor response with serum soluble protein levels via two distinct multiplex (n < 1,000) platforms; (2) response and time-to-event outcomes with germ line SNPs in vascular endothelial growth factor (VEGF)-A and VEGF receptor (VEGFR)3 genes; and (3) response and time-to-event outcomes with tumor immunohistochemistry status for hypoxia-inducible factor 1-alpha (HIF-1α) and carbonic anhydrase-IX or tumor Von Hippel–Lindau (VHL) gene inactivation status. Lower baseline angiopoietin-2 (Ang-2) and higher baseline matrix metalloproteinase-2 (MMP-2) levels were identified by both platforms as statistically significantly associated with tumor response. There were no significant correlations between VEGF-A or VEGFR3 SNPs and outcomes. Progression-free survival was longer for HIF-1α percent of tumor expression groups 0–2 (HIF-1α low) versus 3–4 (HIF-1α high; p = 0.034). There were no significant correlations between outcomes and each VHL inactivation mechanism [mutation (86 % of VHL-inactive patients), methylation (14 %), and large deletion (7 %)] or mechanisms combined. Serum Ang-2 and MMP-2 and tumor HIF-1α were identified as relevant baseline biomarkers of sunitinib activity in advanced RCC, warranting further research into their prognostic versus predictive value. The online version of this article (doi:10.1007/s00280-014-2539-0) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
6.6
作者：
Choueiri, Toni K.;Vaziri, Susan A. J.;Ganapathi, Ram
通讯作者：
Ganapathi, Ram
影响因子：
45.3
作者：
Rini, Brian I.;Michaelson, M. Dror;George, Daniel J.
通讯作者：
George, Daniel J.
影响因子：
45.3
作者：
Xu, Chun-Fang;Bing, Nan X.;Pandite, Lini N.
通讯作者：
Pandite, Lini N.
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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