Division of Oncology, Department of Internal Medicine, Medical University Graz, Austria.
Cancer Biomark. 2010;9(1-6):397-419. doi: 10.3233/CBM-2011-0161.
Metastatic disease is the most important determinant in the clinical management of patients with cancer. Disseminated tumor cells are regarded as a surrogate for early metastatic spread of disease. These cells can be detected in bone marrow aspirates, lymph nodes and peripheral blood, where we refer to them as circulating tumor cells. Detection of disseminated tumor cells represents a great technical challenge, and many different technologies have been developed to enhance the sensitivity and specificity of the testing for these rare events. Different characteristics of tumor cells have been used to establish enrichment methods, including the differential expression of tumor-specific markers on the surface of the cells, the size-based selection of the cells, and other physical properties. Despite technical obstacles, the detection of circulating tumor cells in particular have emerged in recent years as a biomarker with outstanding predictive and prognostic capacity in a number of malignancies including breast, prostate, lung and colorectal cancer. In this text, we provide a comprehensive review of different approaches for enrichment of disseminated and circulating tumor cells and elucidate additional molecular methods for their detection. Further, the clinical significance of disseminated tumor cells detected in various compartments is discussed. Based on recent findings on the biology and heterogeneity of tumor cells, along with development of robust enrichment techniques, we believe that future research will focus less on pure detection but more importantly on detailed molecular characterization of these rare events with the potential impact on design of novel therapeutics.
转移性疾病是癌症患者临床管理中最重要的决定因素。播散的肿瘤细胞被认为是疾病早期转移扩散的替代物。这些细胞可以在骨髓抽吸物、淋巴结和外周血中检测到，我们称之为循环肿瘤细胞。检测播散的肿瘤细胞是一项极具挑战性的技术任务，已经开发了许多不同的技术来提高对这些罕见事件的检测的灵敏度和特异性。肿瘤细胞的不同特征被用于建立富集方法，包括细胞表面肿瘤特异性标志物的差异表达、基于细胞大小的选择以及其他物理特性。尽管存在技术障碍，但近年来，循环肿瘤细胞的检测已成为包括乳腺癌、前列腺癌、肺癌和结直肠癌在内的多种恶性肿瘤中具有出色预测和预后能力的生物标志物。在本文中，我们全面回顾了用于富集播散和循环肿瘤细胞的不同方法，并阐明了用于检测这些细胞的其他分子方法。此外，还讨论了在不同部位检测到的播散肿瘤细胞的临床意义。基于肿瘤细胞生物学和异质性的最新发现，以及强大的富集技术的发展，我们相信未来的研究将不再仅仅关注于纯粹的检测，而是更重要的是对这些罕见事件进行详细的分子特征分析，这可能会对新型治疗药物的设计产生影响。
