Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer.
Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer.
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DOI：
10.1158/2159-8290.cd-12-0222
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发表时间：
2012-11
期刊：
影响因子：
28.2
通讯作者：
Haber DA
中科院分区：
文献类型：
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作者：
Miyamoto DT;Lee RJ;Stott SL;Ting DT;Wittner BS;Ulman M;Smas ME;Lord JB;Brannigan BW;Trautwein J;Bander NH;Wu CL;Sequist LV;Smith MR;Ramaswamy S;Toner M;Maheswaran S;Haber DA
雄激素剥夺疗法（ADT）最初在治疗转移性前列腺癌方面是有效的，而二次激素疗法正在测试抑制去势抵抗性前列腺癌（CRPC）的雄激素受体（AR）再激活。尽管在CRPC中对AR通路抑制剂的反应不同，但没有可靠的生物标志物来指导它们的应用。在这里，我们使用循环肿瘤细胞（ctc）的微流体捕获来测量治疗干预前后的AR信号读数。单细胞免疫荧光分析显示，与CRPC患者的异质性（“AR-on、AR-off和AR-mixed”）CTC群体相比，未治疗患者的CTC特征主要是“AR-on”。一线ADT的启动诱导了ctc从“AR-on”到“AR-off”的深刻转变，而CRPC的二次激素治疗导致了不同的反应。尽管使用醋酸阿比特龙治疗，“ar混合”ctc的存在和“AR-on”细胞的增加与不良治疗结果相关。测量CTCs内治疗诱导的信号反应可能有助于指导前列腺癌的治疗。
Androgen deprivation therapy (ADT) is initially effective in treating metastatic prostate cancer, and secondary hormonal therapies are being tested to suppress androgen receptor (AR) reactivation in castration-resistant prostate cancer (CRPC). Despite variable responses to AR pathway inhibitors in CRPC, there are no reliable biomarkers to guide their application. Here, we used microfluidic capture of circulating tumors cells (CTCs) to measure AR signaling readouts before and after therapeutic interventions. Single cell immunofluorescence analysis revealed predominantly “AR-on” CTC signatures in untreated patients, compared to heterogeneous (“AR-on, AR-off, and AR-mixed”) CTC populations in patients with CRPC. Initiation of first line ADT induced a profound switch from “AR-on” to “AR-off” CTCs, whereas secondary hormonal therapy in CRPC resulted in variable responses. Presence of “AR-mixed” CTCs and increasing “AR-on” cells despite treatment with abiraterone acetate were associated with an adverse treatment outcome. Measuring treatment-induced signaling responses within CTCs may help guide therapy in prostate cancer.