ReviewPost screenPrognostic and predictive relevance of circulating tumor cells in patients with non-small-cell lung cancer
Section snippets
Circulating tumor cells and lung cancer
Circulating tumor cells (CTCs) are rare cancer cells that are supposed to be shed into the bloodstream from the primary tumor or metastatic sites. During the process of malignancy, solid tumors of epithelial origin can evolve from an initial indolent disease into disease with a more aggressive phenotype and then propagate via local expansion into the blood or lymphatic circulation 1, 2. The first description of circulating tumor-like cells was made in 1869 during the autopsy of a metastatic
CTC detection
Over the years, many efforts have been concentrated on the isolation of CTCs from various cancer types, but only recently have reproducible methods been developed that can enumerate and characterize CTCs [22]. Although many techniques for CTC enrichment, taking into account the biological or physical properties of these cells, have been extensively described 23, 24, CellSearch® (Veridex LLC), an epithelial cell adhesion molecule (EpCAM)-based immunomagnetic capture system, and isolation by size
Role of CTCs in the diagnostic performance and prognosis of lung cancer
As previously mentioned, the relevance of CTC detection has been recognized in metastatic breast 7, 8, colorectal [9] and prostate [10] cancers. However, different studies agree in asserting that the identification of CTCs in the blood could also help improve diagnosis and predict prognosis in patients with NSCLC 11, 12, 35.
One of the first efforts to test the feasibility of detecting CTCs in the blood, before and after surgery, was carried out in nine patients, who were undergoing surgery for
Molecular investigations in CTCs
The achievability of determining the presence and cellular localization of specific proteins in CTCs and executing genotyping and molecular characterization has revealed new perspectives for tailoring therapeutic strategies and monitoring treatment efficacy. In selected patients with adenocarcinoma, the therapeutic decision is based on the preliminary evaluation of EGFR mutations and ALK rearrangement, which might help to predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs) and ALK
Role of CTCs as predictors of response to treatment
The role of CTC enumeration has been recognized in a number of studies. However, its correlation with response to therapy requires that its evaluation proves reliable and that it follows the treatment-induced changes over time in accordance with the clinical and instrumental tumor response. To this end, various investigations have shown that the presence of CTCs during the follow-up of patients receiving chemotherapy might provide more information about the treatment response than standard
Concluding remarks
The evidence that CTCs have a significant role at tumor stage and the occurrence of metastasis in NSCLC has led to an awareness of the importance of translating CTC isolation and characterization into clinical practice, improving the techniques to standardize CTC detection. CTCs can be easily obtained through a blood draw and might serve as an additional option to determine prognosis and to monitor disease progression of NSCLC patients during treatment by repeated samplings.
Advances in
References (53)
Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer
Clin. Colorectal Cancer
(2006)Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer
J. Urol.
(2009)Circulating tumor cells as a window on metastasis biology in lung cancer
Am. J. Pathol.
(2011)Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer
Lung Cancer
(2012)Targeting the VEGF pathway: antiangiogenic strategies in the treatment of non-small cell lung cancer
Crit. Rev. Oncol. Hematol.
(2008)Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised Phase 3 trial
Lancet Oncol.
(2012)- et al.
Preclinical strategies targeted at non-small-cell lung cancer signalling pathways with striking translational fallout
Drug Discov. Today
(2013) Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications
Pharmacol. Ther.
(2014)Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker dependent and -independent approaches
J. Thorac. Oncol.
(2012)Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant
Clin. Cancer Res.
(2002)
Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with non-malignant diseases
Clin. Cancer Res.
A case of cancer in which cells similar to those in the tumours were seen in the blood after death
Aust. Med. J.
A systems view of epithelial–mesenchymal transition signaling states
Clin. Exp. Metastasis
Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype
Eur. Respir. Rev.
Molecular mechanisms of epithelial–mesenchymal transition
Nat. Rev. Mol. Cell. Biol.
Circulating tumor cells, disease progression, and survival in metastatic breast cancer
N. Engl. J. Med.
Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer
J. Clin. Oncol.
Cancer statistics, 2013
CA Cancer J Clin.
Future scenarios for the treatment of advanced non-small cell lung cancer: focus on taxane-containing regimens
Oncologist
Pemetrexed for the treatment of non-small cell lung cancer
Expert Opin. Pharmacother.
Crizotinib versus chemotherapy in advanced ALK-positive lung cancer
N. Engl. J. Med.
Genetically abnormal circulating cells in lung cancer patients: an antigen-independent fluorescence in situ hybridization-based case–control study
Cancer Res.
Simultaneous phenotypic and genetic characterization of single circulating tumor cells from colon cancer patients
Histol. Histopathol.
Enrichment, detection and clinical significance of circulating tumor cells
Lab Chip
Considerations in the development of circulating tumor cell technology for clinical use
J. Transl. Med.
Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146
Breast Cancer Res. Treat.
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2021, Lung CancerCitation Excerpt :The trend towards poor outcome may not be strong enough for high CCSC and CTC levels in outcome prediction. Previous studies have used a wide range of cutoff values of CTCs from 1 per 7.5 mL blood to 50 per 10 mL blood. [41] Further trial with larger sample size is needed to confirm our data as well as validate the cut-off levels.
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2021, Journal of EthnopharmacologyCitation Excerpt :Circulating tumor cells in the peripheral blood have not attracted much attention. Recent studies have shown that CTCs can be applied to predict disease progression and survival (Alama et al., 2014; Zhou et al., 2017). Multiple lines of evidence indicate that CTCs are already present even before the primary cancer can be detected (Hu et al., 2019; Ilie et al., 2014).
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2019, Biosensors and BioelectronicsCitation Excerpt :According to previous studies, up to 90% of patients die from metastasis to distant sites rather than from the primary tumor (Weiss, 2000). Thus, the presence of CTCs is highly related to disease progression and has been shown to be correlated with prognosis in several cancers, including breast cancer (Rack et al., 2014), lung cancer (Alama et al., 2014; Chen and Xu, 2014), gastric cancer (Zheng et al., 2017), colorectal cancer (Negin and Cohen, 2010), head and neck cancers (Kulasinghe et al., 2015), especially NPC (He et al., 2017; Si et al., 2016; Wu et al., 2017), and many other malignancies. It has also been proposed that tumor burden affects the level of released CTCs, and an increase in tumor burden might increase the number of CTCs (Chen et al., 2018).
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2017, Lung CancerCitation Excerpt :The prognostic significance of CTCs has already been proved in metastatic breast, colorectal and prostate cancer [5–7]. Furthermore, recent experiences indicate that CTCs could play a role also in non small cell lung cancer (NSCLC) for diagnosis, biological characterization and disease monitoring [8,9]. CTCs could be particularly useful in this clinical setting since tumor tissue obtained from biopsies is often insufficient for a comprehensive histopatological-molecular analysis, patients are not always suitable to receive multiple biopsies and because of the lack of reliable tumor markers.
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