| Literature DB >> 24880617 |
Cassandra L Hodgkinson1, Christopher J Morrow1, Yaoyong Li2, Robert L Metcalf3, Dominic G Rothwell3, Francesca Trapani3, Radoslaw Polanski3, Deborah J Burt3, Kathryn L Simpson3, Karen Morris3, Stuart D Pepper4, Daisuke Nonaka5, Alastair Greystoke6, Paul Kelly3, Becky Bola3, Matthew G Krebs3, Jenny Antonello3, Mahmood Ayub3, Suzanne Faulkner3, Lynsey Priest3, Louise Carter3, Catriona Tate3, Crispin J Miller7, Fiona Blackhall8, Ged Brady1, Caroline Dive1.
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.Entities:
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Year: 2014 PMID： 24880617 DOI： 10.1038/nm.3600
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440