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

First Author  Hodgkinson CL Year  2014
Journal  Nat Med Volume  20
Issue  8 Pages  897-903
PubMed ID  24880617 Mgi Jnum  J:227610
Mgi Id  MGI:5701614 Doi  10.1038/nm.3600
Citation  Hodgkinson CL, et al. (2014) Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat Med 20(8):897-903
abstractText  Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor with early dissemination and dismal prognosis, accounts for 15-20% of lung cancer cases and approximately 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.
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