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Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer

機(jī)譯：雄激素受體信號(hào)傳導(dǎo)在循環(huán)腫瘤細(xì)胞中作為激素反應(yīng)性前列腺癌的標(biāo)志物

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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.
機(jī)譯：雄激素剝奪療法（ADT）最初可有效治療轉(zhuǎn)移性前列腺癌，并且正在進(jìn)行二次激素療法以抑制去勢抵抗性前列腺癌（CRPC）中的雄激素受體（AR）活化。盡管在CRPC中對(duì)AR途徑抑制劑的反應(yīng)不同，但尚無可靠的生物標(biāo)志物來指導(dǎo)其應(yīng)用。在這里，我們使用微流控捕獲的循環(huán)腫瘤細(xì)胞（CTC）來測量治療性干預(yù)前后的AR信號(hào)讀數(shù)。單細(xì)胞免疫熒光分析顯示，與CRPC患者的異質(zhì)（“ AR-on，AR-off和AR-mixed”）CTC群體相比，未經(jīng)治療的患者主要表現(xiàn)為“ AR-on” CTC特征。一線ADT的啟動(dòng)引起了從“ AR-on”到“ AR-off” CTC的深刻轉(zhuǎn)變，而CRPC中的二次激素治療導(dǎo)致反應(yīng)不同。盡管使用醋酸阿比特龍治療，“ AR混合” CTC的存在和“ AR-on”細(xì)胞的增加與不良的治療結(jié)果相關(guān)。測量CTC中治療引起的信號(hào)傳導(dǎo)反應(yīng)可能有助于指導(dǎo)前列腺癌的治療。

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