Association of AR-V7 on Circulating Tumor Cells as a Treatment-Specific Biomarker With Outcomes and Survival in Castration-Resistant Prostate Cancer.
Association of AR-V7 on Circulating Tumor Cells as a Treatment-Specific Biomarker With Outcomes and Survival in Castration-Resistant Prostate Cancer.
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DOI：
10.1001/jamaoncol.2016.1828
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发表时间：
2016-11-01
期刊：
影响因子：
28.4
通讯作者：
Dittamore, Ryan
中科院分区：
文献类型：
--
作者：
Scher, Howard I.;Lu, David;Schreiber, Nicole A.;Louw, Jessica;Graf, Ryon P.;Vargas, Hebert A.;Johnson, Ann;Jendrisak, Adam;Bambury, Richard;Danila, Daniel;McLaughlin, Brigit;Wahl, Justin;Greene, Stephanie B.;Heller, Glenn;Marrinucci, Dena;Fleisher, Martin;Dittamore, Ryan
治疗转移性去势抵抗性前列腺癌 (mCRPC) 的一个关键决定是何时给予雄激素受体信号 (ARS) 抑制剂或紫杉烷。确定治疗前核雄激素受体剪接变体 7 (AR-V7) 蛋白在循环肿瘤细胞 (CTC) 上的表达和定位是否是 ARS 抑制剂和紫杉烷之间反应和结果的治疗特异性标志物。在纪念斯隆凯特琳癌症中心进行的这项横断面队列研究中，考虑了 265 名患有进展性 mCRPC 且正在接受治疗改变的男性； 86 人被排除，因为他们没有开始 ARS 或紫杉烷治疗； 18 名患者因处理时间限制而被排除，留下 161 名患者进行分析。 2012 年 12 月至 2015 年 3 月期间，在新系列全身治疗前立即从进展性 mCRPC 患者身上采集血液并进行处理。患者随访长达 3 年。前列腺特异性抗原 (PSA) 反应、接受治疗的时间、影像学无进展生存期 (rPFS) 和总生存期 (OS)。总体而言，在从 161 名 mCRPC 男性中前瞻性收集的 193 份血液样本中，191 份可评估（128 份前 ARS 抑制剂和 63 份前紫杉烷）。在 34 个样本 (18%) 中发现 AR-V7 阳性 CTC，其中一线样本为 3%，二线样本为 18%，三线或更高线样本为 31%。与没有 AR-V7 阳性 CTC 的患者相比，在 ARS 抑制前样本中含有 AR-V7 阳性 CTC 的患者具有耐药性治疗后 PSA 变化 (PTPC)、更短的 rPFS、更短的治疗时间和更短的 OS。总体而言，在 ARS 抑制之前，112 个样本中的 65 个样本 (58%) 中发现了耐药 PTPC，而没有检测到 AR-V7 阳性 CTC。对于治疗前有或没有接受紫杉烷治疗的 AR-V7 阳性 CTC 的患者，OS 存在统计学显着性差异，但 PTPC、治疗时间或 rPFS 没有显着差异。调整与生存相关的基线因素的多变量模型显示，当治疗前检测到 AR-V7 阳性 CTC 时，紫杉烷类药物相对于 ARS 抑制剂具有更好的 OS（风险比，0.24；95%CI，0.10-0.57；P = 0.035）。结果验证了 mCRPC 男性中 AR-V7 蛋白的 CTC 核表达作为治疗特异性生物标志物，与临床实践中紫杉烷治疗优于 ARS 导向治疗的生存率相关。在前瞻性研究中继续检查这种生物标志物将进一步有助于临床应用。
A critical decision in the management of metastatic castration-resistant prostate cancer (mCRPC) is when to administer an androgen receptor signaling (ARS) inhibitor or a taxane. To determine if pretherapy nuclear androgen-receptor splice variant 7 (AR-V7) protein expression and localization on circulating tumor cells (CTCs) is a treatment-specific marker for response and outcomes between ARS inhibitors and taxanes. For this cross-sectional cohort study at Memorial Sloan Kettering Cancer Center, 265 men with progressive mCRPC undergoing a change in treatment were considered; 86 were excluded because they were not initiating ARS or taxane therapy; and 18 were excluded for processing time constraints, leaving 161 patients for analysis. Between December 2012 and March 2015, blood was collected and processed from patients with progressive mCRPC immediately prior to new line of systemic therapy. Patients were followed up to 3 years. Prostate-specific antigen (PSA) response, time receiving therapy, radiographic progression-free survival (rPFS), and overall survival (OS). Overall, of 193 prospectively collected blood samples from 161 men with mCRPC, 191 were evaluable (128 pre-ARS inhibitor and 63 pretaxane). AR-V7–positive CTCs were found in 34 samples (18%), including 3% of first-line, 18% of second-line, and 31% of third- or greater line samples. Patients whose samples had AR-V7–positive CTCs before ARS inhibition had resistant posttherapy PSA changes (PTPC), shorter rPFS, shorter time on therapy, and shorter OS than those without AR-V7–positive CTCs. Overall, resistant PTPC were seen in 65 of 112 samples (58%) without detectable AR-V7–positive CTCs prior to ARS inhibition. There were statistically significant differences in OS but not in PTPC, time on therapy, or rPFS for patients with or without pretherapy AR-V7–positive CTCs treated with a taxane. A multivariable model adjusting for baseline factors associated with survival showed superior OS with taxanes relative to ARS inhibitors when AR-V7–positive CTCs were detected pretherapy (hazard ratio, 0.24; 95%CI, 0.10–0.57; P = .035). The results validate CTC nuclear expression of AR-V7 protein in men with mCRPC as a treatment-specific biomarker that is associated with superior survival on taxane therapy over ARS-directed therapy in a clinical practice setting. Continued examination of this biomarker in prospective studies will further aid clinical utility.
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DOI：
10.1038/nrclinonc.2013.30
发表时间：
2013-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.8
作者：
Punnoose EA;Ferraldeschi R;Szafer-Glusman E;Tucker EK;Mohan S;Flohr P;Riisnaes R;Miranda S;Figueiredo I;Rodrigues DN;Omlin A;Pezaro C;Zhu J;Amler L;Patel P;Yan Y;Bales N;Werner SL;Louw J;Pandita A;Marrinucci D;Attard G;de Bono J
通讯作者：
de Bono J
影响因子：
11.1
作者：
Joosse SA;Gorges TM;Pantel K
通讯作者：
Pantel K
DOI：
10.1056/nejmoa1315815
发表时间：
2014-09-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Antonarakis ES;Lu C;Wang H;Luber B;Nakazawa M;Roeser JC;Chen Y;Mohammad TA;Chen Y;Fedor HL;Lotan TL;Zheng Q;De Marzo AM;Isaacs JT;Isaacs WB;Nadal R;Paller CJ;Denmeade SR;Carducci MA;Eisenberger MA;Luo J
通讯作者：
Luo J
影响因子：
4.6
作者：
Qu Y;Dai B;Ye D;Kong Y;Chang K;Jia Z;Yang X;Zhang H;Zhu Y;Shi G
通讯作者：
Shi G