Circulating Tumor Cell and Cell-free Circulating Tumor DNA in Lung Cancer

Abstract

Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer.

The Prognostic Role of Circulating Tumor Cells (CTCs) in Lung Cancer

“…In order to detach from the primary tumor and disseminate into the blood, cells must undergo a cellular process known as epithelial-mesenchymal transition (EMT) ( 18 ). EMT enables tumor cells to become motile and enhances migratory capabilities which in effect allows cells to penetrate into the lymph vasculature and circulate as single or clusters of circulating tumor cells (CTCs) ( 19 ). Whilst in blood, CTCs exist in a dynamic EMT state ( 20 ).…”

“…Use of CTCs as a liquid biopsy is promising for serial assessment of tumor evolution during the course of the disease and during systemic treatment in a less invasive, real-time manner, by a simple blood draw ( 19 , 43 ). This liquid biopsy also provides potential for the early diagnosis of cancer and valuable insights into tumor heterogeneity and genomic diversity for the early diagnosis of cancer and guidance of clinical treatment ( 44 , 45 ).…”

Longitudinal Change of Circulating Tumor Cells During Chemoradiation Therapy and Its Correlation with Prognosis in Advanced Non-Small Cell Lung Cancer Patients

“…Knowledge of metastasis may help understand the biology of CTCs in NSCLC [7,14,15]. Metastasis is an extremely complex and multistep process, in which the tumor cells must undergo a cellular process termed as epithelial mesenchymal transition (EMT) [7].…”

“…Metastasis is an extremely complex and multistep process, in which the tumor cells must undergo a cellular process termed as epithelial mesenchymal transition (EMT) [7]. EMT enables the tumor cells to be motile, and also allows cells to penetrate into the lymph vessels and to circulate as a single or clusters of CTCs [7,14,15]. Then, CTCs spread to distant organs and facilitate the formation of secondary sites of the tumor disease, moreover, CTCs may form disseminating tumor cells known as a settlement of CTCs in other organs, which may stay in a quiescence state or lead to an observable metastasis [16].…”

Performance evaluation of detecting circulating tumor cells and tumor cells in bronchoalveolar lavage fluid in diagnosis of peripheral lung cancer

“…CTC refers to a group of tumor cell that detach from the primary or metastatic foci of solid tumors, and spontaneously enter the peripheral blood circulation, whereas CTC is commonly absent in normal individuals. CTCs detection, a novel non-invasive method for identifying of malignant lesion, is reportedly to be applicable for the diagnosis of solid malignant tumors (8). The chromosome enumeration probe 8 (CEP8) were amplificated frequently in lung cancer specimens with 81% amplification percentage (9).…”