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

Hodgkinson, Cassandra L
; 
Morrow, Christopher J
; 
Li, Yaoyong
; 
Metcalf, Robert
; 
Rothwell, Dominic G
; 
Trapani, Francesca
; 
Polański, Radosław
; 
Burt, Deborah J
; 
Simpson, Kathryn L
; 
Morris, Karen
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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.
Authors
Hodgkinson, Cassandra L
Morrow, Christopher J
Li, Yaoyong
Metcalf, Robert
Rothwell, Dominic G
Trapani, Francesca
Polański, Radosław
Burt, Deborah J
Simpson, Kathryn L
Morris, Karen
Pepper, Stuart D
Nonaka, Daisuke
Greystoke, Alastair
Kelly, Paul
Bola, Becky
Krebs, Matthew G
Antonello, Jenny
Ayub, Mahmood
Faulkner, Suzanne
Priest, Lynsey
Carter, Louise
Tate, Catriona
Miller, Crispin J
Blackhall, Fiona H
Brady, Ged
Dive, Caroline
Affiliation
Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.
Description
Date
2014-06-01
Publisher
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All Christie Publications
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Type
Article
Citation
Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. 2014: Nat Med
Journal Title
Journal ISSN
Volume Title
URI
http://hdl.handle.net/10541/321831
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