Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer.
Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer.
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DOI：
10.1001/jamaoncol.2018.1621
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发表时间：
2018-09-01
期刊：
影响因子：
28.4
通讯作者：
Heller G
中科院分区：
文献类型：
--
作者：
Scher HI;Graf RP;Schreiber NA;Jayaram A;Winquist E;McLaughlin B;Lu D;Fleisher M;Orr S;Lowes L;Anderson A;Wang Y;Dittamore R;Allan AL;Attard G;Heller G
用于确定是否使用雄激素受体信号传导（ARS）抑制剂或紫杉烷治疗转移性去势抵抗性前列腺癌（mCRPC）患者的血液检查是一项未满足的医疗需求。确定循环肿瘤细胞（CTC）中定位于细胞核的雄激素受体剪接变体7（AR-V7）蛋白的经验证测定是否可以预测接受紫杉烷类与ARS抑制剂治疗的mCRPC患者的差异总生存期（OS）。设盲相关研究。患者随访4.3年。Memorial Sloan Kettering癌症中心（美国）、癌症研究所（英国）和伦敦健康科学中心（加拿大）的多机构门诊。考虑了在286次药物暴露前抽取的248例mCRPC患者的横断面队列。分析亚组包括142例在ARS抑制剂或紫杉烷类药物二线或以上全身治疗进展性mCRPC前抽取的患者。ARS抑制剂或紫杉烷治疗后的OS与治疗前AR-V7状态相关。对于通过常规预后因素指定为高风险的mCRPC患者，接受紫杉烷类治疗的AR-V7阳性患者的OS优于接受ARS抑制剂治疗的患者，接受ARS抑制剂治疗的AR-V7阴性患者的OS优于接受紫杉烷类治疗的患者。CTC中的核定位AR-V7蛋白可以识别紫杉烷化疗比ARS抑制剂（阿比特龙、恩杂鲁胺、阿帕鲁胺）生存时间更长的患者。
A blood test to determine whether to treat patients with metastatic castration-resistant prostate cancer (mCRPC) with an androgen receptor signaling (ARS) inhibitor or taxane is an unmet medical need. To determine whether a validated assay for androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells (CTCs) that is localized to the nucleus can predict differential overall survival (OS) in mCRPC patients treated with taxanes vs. ARS inhibitors. Blinded correlative study. Patients were followed up to 4.3 years. Multi-institution outpatient clinics at Memorial Sloan Kettering Cancer Center (USA), Institute for Cancer Research (UK) and London Health Sciences Centre (Canada). A cross-sectional cohort of 248 patients with mCRPC drawn prior to 286 drug exposures were considered. The analysis subset included 142 patients drawn prior to administration of ARS inhibitors or taxanes at the second or greater line of systemic therapy for progressing mCRPC. OS following an ARS inhibitor or taxane in relation to pretherapy AR-V7 status. For mCRPC patients designated as high-risk by conventional prognostic factors, AR-V7-positive patients treated with taxanes have superior OS relative to those treated with ARS inhibitors, and AR-V7-negative patients treated with ARS inhibitors have superior OS relative to taxane-treated patients. Nuclear-localized AR-V7 protein in CTCs can identify patients who may live longer on taxane chemotherapy than on ARS inhibitors (abiraterone, enzalutamide, apalutamide).
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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：
16.6
作者：
通讯作者：
--
影响因子：
11.2
作者：
Scher HI;Graf RP;Schreiber NA;McLaughlin B;Jendrisak A;Wang Y;Lee J;Greene S;Krupa R;Lu D;Bamford P;Louw JE;Dugan L;Vargas HA;Fleisher M;Landers M;Heller G;Dittamore R
通讯作者：
Dittamore R
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