Alix-Panabières Catherine, Pierga Jean-Yves
Laboratoire cellules circulantes rares humaines, département de biopathologie cellulaire et tissulaire des tumeurs, Institut de recherche en biothérapie, Hôpital Saint-Éloi, CHRU, 80, avenue Augustin-Fliche, Montpellier, France, Université Montpellier 1, EA2415 Épidémiologie, biostatistiques et santé publique, Institut Universitaire de Recherche Clinique, 641, Avenue du Doyen Gaston Giraud, 34093 Montpellier, France.
Laboratoire des biomarqueurs circulants, SIRIC et département d'oncologie médicale de l'Institut Curie, 26, rue d'Ulm, 75005 Paris, France, Université Paris-Descartes, 12, rue de l'École-de-Médecine, 75270 Paris Cedex 06, France.
Bull Cancer. 2014 Jan 1;101(1):17-23. doi: 10.1684/bdc.2014.1883.
The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with more than 400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include: a) estimation of the risk for metastatic relapse or metastatic progression (prognostic information); b) stratification and real-time monitoring of therapies; c) identification of therapeutic targets and resistance mechanisms; and d) understanding metastasis development in cancer patients. This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecular characterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelial-mesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells). A considerable number of promising CTC detection techniques have been developed in recent years. The analytical specificity and clinical utility of these methods must be demonstrated in large prospective multicenter studies to reach the high level of evidence required for their introduction into clinical practice.
循环肿瘤细胞（CTC）的检测及分子特征分析是转化癌症研究中最活跃的领域之一，已有400多项临床研究将CTC作为生物标志物。对CTC的研究目的包括：a）评估转移复发或转移进展的风险（预后信息）；b）治疗的分层及实时监测；c）确定治疗靶点和耐药机制；d）了解癌症患者转移的发生情况。本综述聚焦于用于富集和检测CTC的技术。我们概述并讨论了目前基于利用CTC物理和生物学特性的技术。最近已开发出许多创新技术来改进CTC检测方法，包括CTC微芯片、过滤装置、定量逆转录PCR检测法和自动显微镜系统。然而，分子特征研究表明，CTC非常异质性，这一发现凸显了需要采用多重方法来捕获所有相关的CTC亚群。因此，我们强调当前在提高经历上皮-间质转化的CTC的产量和检测方面所面临的挑战。然而，提高检测分析灵敏度可能会导致分析特异性降低（例如，通过检测循环中的正常上皮细胞）。近年来已开发出大量有前景的CTC检测技术。这些方法的分析特异性和临床实用性必须在大型前瞻性多中心研究中得到证实，以达到将其引入临床实践所需的高水平证据。
