Circulating tumor cells as biomarkers in prostate cancer.
Circulating tumor cells as biomarkers in prostate cancer.
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DOI：
10.1158/1078-0432.ccr-10-2650
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发表时间：
2011-06-15
期刊：
影响因子：
--
通讯作者：
Scher HI
中科院分区：
文献类型：
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作者：
Danila DC;Fleisher M;Scher HI
前列腺癌药物开发和患者管理中未满足的需求是在考虑治疗时监测治疗获益和识别肿瘤中感兴趣的靶标的能力。本文综述了在去势抵抗性前列腺癌（CRPC）患者中建立分析有效的生物标志物，强调目前临床使用的生物标志物，循环肿瘤细胞（CTC）。肿瘤学生物标志物鉴定计划为这些研究提供了路线图，如果遵循，将有助于将这些类型的测定纳入临床决策。基线和治疗后的CTC计数是生存的预后，没有阈值效应，并且细胞脱落到循环中代表肿瘤的固有特性，与疾病程度不同。目前正在使用新型抗雄激素治疗醋酸阿比特龙和MDV 3100的大型III期试验中测试监测治疗期间CTC变化作为生存期疗效-反应替代生物标志物的临床效用。分子生物标志物可以在CTC中表征为肿瘤对治疗方式敏感性的潜在预测生物标志物。此外，我们还讨论了从更多患者中富集和表征CTC的新技术，以及CTC在确定预后和监测治疗效果方面的潜在临床用途，以及作为组织来源来识别药物敏感性的预测标志物以指导治疗选择。需要围绕生物标志物本身及其应用的特定临床背景进行前瞻性研究，以进一步评估这些和新标志物在临床实践中的作用。
Unmet needs in prostate cancer drug development and patient management are the ability to monitor treatment benefit and to identify the target of interest in a tumor at the time treatment is being considered. This review focuses on establishing analytical valid biomarkers for specific contexts of use in patients with castration-resistant prostate cancer (CRPC), emphasizing a biomarker currently in clinical use, circulating tumor cells (CTC). The Oncology Biomarker Qualification Initiative provides a road map for these investigations, which, if followed, will facilitate the incorporation of these types of assays into clinical decision-making. CTC enumeration at baseline and post-treatment is prognostic of survival, with no threshold effect, and the shedding of cells into the circulation represents an intrinsic property of the tumor, distinct from extent of disease. The clinical utility of monitoring CTC changes with treatment as an efficacy-response surrogate biomarker of survival is currently being tested in large phase III trials with the novel antiandrogen therapies abiraterone acetate and MDV3100. Molecular biomarkers can be characterized in CTC as potential predictive biomarkers of tumor sensitivity to a therapeutic modality. Additionally, we discuss novel technologies to enrich and characterize CTC from more patients, and the potential clinical uses of CTC's in determining prognosis and monitoring treatment effects, and as a source of tissue to identify predictive markers of drug sensitivity to guide treatment selection. Prospective studies, designed around the biomarker itself and the specific clinical context for which it is applied, are needed to further assess the role of these and novel markers in clinical practice.