Authors' Affiliations: Division of Clinical Studies, The Institute of Cancer Research; Drug Development Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom; Kantonsspital St. Gallen, Department of Medical Oncology, Gallen, Switzerland; and Spanish National Cancer Research Centre, Madrid, SpainAuthors' Affiliations: Division of Clinical Studies, The Institute of Cancer Research; Drug Development Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom; Kantonsspital St. Gallen, Department of Medical Oncology, Gallen, Switzerland; and Spanish National Cancer Research Centre, Madrid, Spain.
Authors' Affiliations: Division of Clinical Studies, The Institute of Cancer Research; Drug Development Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom; Kantonsspital St. Gallen, Department of Medical Oncology, Gallen, Switzerland; and Spanish National Cancer Research Centre, Madrid, Spain.
Clin Cancer Res. 2014 May 15;20(10):2553-68. doi: 10.1158/1078-0432.CCR-13-2664.
One of the most promising developments in translational cancer medicine has been the emergence of circulating tumor cells (CTC) as a minimally invasive multifunctional biomarker. CTCs in peripheral blood originate from solid tumors and are involved in the process of hematogenous metastatic spread to distant sites for the establishment of secondary foci of disease. The emergence of modern CTC technologies has enabled serial assessments to be undertaken at multiple time points along a patient's cancer journey for pharmacodynamic (PD), prognostic, predictive, and intermediate endpoint biomarker studies. Despite the promise of CTCs as multifunctional biomarkers, there are still numerous challenges that hinder their incorporation into standard clinical practice. This review discusses the key technical aspects of CTC technologies, including the importance of assay validation and clinical qualification, and compares existing and novel CTC enrichment platforms. This article discusses the utility of CTCs as a multifunctional biomarker and focuses on the potential of CTCs as PD endpoints either directly via the molecular characterization of specific markers or indirectly through CTC enumeration. We propose strategies for incorporating CTCs as PD biomarkers in translational clinical trials, such as the Pharmacological Audit Trail. We also discuss issues relating to intrapatient heterogeneity and the challenges associated with isolating CTCs undergoing epithelial-mesenchymal transition, as well as apoptotic and small CTCs. Finally, we envision the future promise of CTCs for the selection and monitoring of antitumor precision therapies, including applications in single CTC phenotypic and genomic profiling and CTC-derived xenografts, and discuss the promises and limitations of such approaches. See ALL articles in this CCR focus section, "Progress in pharmacodynamic endpoints."
循环肿瘤细胞（CTC）作为一种微创多功能生物标志物的出现，是转化癌症医学中最有前途的进展之一。外周血中的 CTC 来源于实体瘤，并参与血液转移扩散到远处部位以建立疾病继发灶的过程。现代 CTC 技术的出现使得能够在患者癌症治疗过程中的多个时间点进行连续评估，用于药效学（PD）、预后、预测和中间终点生物标志物研究。尽管 CTC 作为多功能生物标志物具有很大的应用前景，但仍存在许多阻碍其纳入标准临床实践的挑战。本文讨论了 CTC 技术的关键技术方面，包括检测方法验证和临床资格的重要性，并比较了现有的和新型的 CTC 富集平台。本文讨论了 CTC 作为多功能生物标志物的实用性，并重点讨论了 CTC 作为 PD 终点的潜力，无论是通过对特定标志物的分子特征进行直接分析，还是通过 CTC 计数进行间接分析。我们提出了将 CTC 作为 PD 生物标志物纳入转化临床试验的策略，例如药物审核追踪。我们还讨论了与患者内异质性以及分离经历上皮-间充质转化、凋亡和小 CTC 相关的挑战有关的问题。最后，我们设想了 CTC 在选择和监测抗肿瘤精准治疗中的未来前景，包括在单个 CTC 表型和基因组分析以及 CTC 衍生的异种移植物中的应用，并讨论了这些方法的优缺点。查看 CCR 焦点部分“药效学终点的进展”中的所有文章。
