Journal
JOURNAL OF THORACIC DISEASE
Volume 10, Issue 7, Pages E570-E576Publisher
AME PUBL CO
DOI: 10.21037/jtd.2018.06.38
Keywords
Non-small cell lung cancer (NSCLC); epidermal growth factor receptor (EGFR); circulating tumor cells (CTCs); epithelial cell adhesion molecule-positive and epithelial cell adhesion molecule-low/negative (EpCAM pos and EpCAM low/neg); circulating tumor DNA (ctDNA); liquid biopsy
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Funding
- Italian Ministry of Health [GR-2010-2303193A]
- Innovative Medicine Initiative Joint Undertaking CANCER-ID [115749]
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In non-small cell lung cancer (NSCLC), there is a consensus regarding the use of liquid biopsy, generally, to detect druggable mutations and, in particular, to monitor tyrosine kinase inhibitor (TKI) treatments. However, whether circulating tumor cells (CTCs) are better tools than cell-free DNA (cfDNA), is still a matter of debate, mainly concerning which antigen(s) we should use to investigating simultaneously both epithelial and epithelial-to-mesenchymal transient (EMT) phenotype in the same sample of CTCs. To address this item, we exploited here a single-tube liquid biopsy, to detect both epithelial cell adhesion molecule (EpCAM)-positive CTCs and EpCAM-low/negative CTCs, because down-modulation of EpCAM is considered the first step in EMT. Furthermore, we analyzed the DNA from CTCs of four different phenotypes (ctcDNA), according to their EpCAM expression and cytokeratin pattern, and circulating tumor DNA (ctDNA) by droplet digital PCR (ddPCR), in order to disclose activating and resistance-driving mutations. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution.
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