London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 4L6, Canada.
Cancers (Basel). 2014 Mar 13;6(1):595-624. doi: 10.3390/cancers6010595.
Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch® system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a "real-time liquid biopsy" that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing.
虽然循环肿瘤细胞 (CTCs) 在一个多世纪前就被首次观察到,但直到最近,由于缺乏敏感的方法学,这些细胞仍无法进行详细研究。然而,技术的进步现在已经促进了使用各种方法对 CTCs 的鉴定、计数和特征分析。支持 CTCs 在临床决策中应用的大多数证据都与使用 CellSearch®系统进行计数以及与预后的相关性有关。越来越多的证据还表明,CTC 监测可以根据治疗前后 CTC 水平的比较,为患者治疗反应提供早期指示。然而,CTC 为肿瘤学提供的最大潜力可能在于分子特征分析。如果临床治疗决策基于转移性细胞的分子特征,而不仅仅是基于原发性肿瘤的特征,那么决策可能会更有效。CTC 的分子特征分析(可以以微创的方式重复分离)提供了“实时液体活检”的机会,从而可以评估遗传漂移、研究分子疾病演变,并确定可操作的基因组特征。这篇综述重点介绍了该领域的最新进展,包括涉及免疫表型分析、荧光原位杂交 (FISH)、多重 RT-PCR、微阵列和基因组测序的方法。