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Nat Med. 2014 Aug;20(8):897-903. doi: 10.1038/nm.3600. Epub 2014 Jun 1.

Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer.

Author information

1
1] Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK. [2].
2
Computational Biology Support Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.
3
Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.
4
Molecular Biology Core Facility, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.
5
The Christie NHS Foundation Trust, Manchester, UK.
6
1] Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK. [2] The Christie NHS Foundation Trust, Manchester, UK. [3] Institute of Cancer Sciences, University of Manchester, Manchester, UK.
7
1] Computational Biology Support Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK. [2] RNA Biology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.
8
1] The Christie NHS Foundation Trust, Manchester, UK. [2] Institute of Cancer Sciences, University of Manchester, Manchester, UK. [3].

Abstract

Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor with early dissemination and dismal prognosis, accounts for 15-20% of lung cancer cases and ∼200,000 deaths each year. Most cases are inoperable, and biopsies to investigate SCLC biology are rarely obtainable. Circulating tumor cells (CTCs), which are prevalent in SCLC, present a readily accessible 'liquid biopsy'. Here we show that CTCs from patients with either chemosensitive or chemorefractory SCLC are tumorigenic in immune-compromised mice, and the resultant CTC-derived explants (CDXs) mirror the donor patient's response to platinum and etoposide chemotherapy. Genomic analysis of isolated CTCs revealed considerable similarity to the corresponding CDX. Most marked differences were observed between CDXs from patients with different clinical outcomes. These data demonstrate that CTC molecular analysis via serial blood sampling could facilitate delivery of personalized medicine for SCLC. CDXs are readily passaged, and these unique mouse models provide tractable systems for therapy testing and understanding drug resistance mechanisms.

PMID:
24880617
DOI:
10.1038/nm.3600
[Indexed for MEDLINE]

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