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

Cassandra Hodgkinson, Christopher Morrow, Yaoyong Li, Robert Metcalf, Dominic G. Rothwell, Francesca Trapani, Radoslaw Polanski, Deborah J Burt, Kathryn L Simpson, Karen Morris, Stuart D Pepper, Daisuke Nonaka, Alastair Greystoke, Paul Kelly, Becky Bola, Matthew G. Krebs, Jenny Antonello, Mahmood Ayub, Suzanne Faulkner, Lynsey PriestLouise Carter, Catriona Tate, Crispin J. Miller, Fiona Blackhall, Ged Brady, Caroline Dive

Research output: Contribution to journalArticlepeer-review


Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor with early dissemination and dismal prognosis, accounts for 15-20% of lung cancer cases and â ̂1/4200,000 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. © 2014 Nature America, Inc.
Original languageEnglish
Pages (from-to)897-903
Number of pages6
JournalNature Medicine
Issue number8
Publication statusPublished - Aug 2014

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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