Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer

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• 作者：John D. O’ ; Flaherty^a ; ^{joflaherty@stjames.ie} ; ^{jdoflaherty@gmail.com} ; Steven Gray^a ; Derek Richard^b ; Dean Fennell^c ; John J. O’ ; Leary^d ; Fiona H. Blackhall^e ; Kenneth J. O’ ; Byrne^a
• 关键词：Circulating tumour cells (CTCs) ; Circulating tumour microemboli (CTM) ; Non-small cell lung cancer ; Small cell lung cancer ; Biomarker ; Liquid biopsy ; Metastasis ; Epithelial mesenchymal transition (EMT)
• 刊名：Lung Cancer
• 出版年：2012
• 期刊代码：187_01695002
• 类别：med
• 出版时间：April, 2012
• 卷：76
• 期：1
• 页码：19-25
• 文件大小：285 K

摘要

Circulating tumour cells (CTCs) have attracted much recent interest in cancer research as a potential biomarker and as a means of studying the process of metastasis. It has long been understood that metastasis is a hallmark of malignancy, and conceptual theories on the basis of metastasis from the nineteenth century foretold the existence of a tumour 鈥渟eed鈥?which is capable of establishing discrete tumours in the 鈥渟oil鈥?of distant organs. This prescient 鈥渟eed and soil鈥?hypothesis accurately predicted the existence of CTCs; microscopic tumour fragments in the blood, at least some of which are capable of forming metastases. However, it is only in recent years that reliable, reproducible methods of CTC detection and analysis have been developed. To date, the majority of studies have employed the CellSearch鈩?system (Veridex LLC), which is an immunomagnetic purification method. Other promising techniques include microfluidic filters, isolation of tumour cells by size using microporous polycarbonate filters and flow cytometry-based approaches. While many challenges still exist, the detection of CTCs in blood is becoming increasingly feasible, giving rise to some tantalizing questions about the use of CTCs as a potential biomarker. CTC enumeration has been used to guide prognosis in patients with metastatic disease, and to act as a surrogate marker for disease response during therapy. Other possible uses for CTC detection include prognostication in early stage patients, identifying patients requiring adjuvant therapy, or in surveillance, for the detection of relapsing disease. Another exciting possible use for CTC detection assays is the molecular and genetic characterization of CTCs to act as a 鈥渓iquid biopsy鈥?representative of the primary tumour. Indeed it has already been demonstrated that it is possible to detect HER2, KRAS and EGFR mutation status in breast, colon and lung cancer CTCs respectively. In the course of this review, we shall discuss the biology of CTCs and their role in metastagenesis, the most commonly used techniques for their detection and the evidence to date of their clinical utility, with particular reference to lung cancer.