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dc.contributor.authorHodgkinson, Cassandra L
dc.contributor.authorMorrow, Christopher J
dc.contributor.authorLi, Yaoyong
dc.contributor.authorMetcalf, Robert
dc.contributor.authorRothwell, Dominic G
dc.contributor.authorTrapani, Francesca
dc.contributor.authorPolański, Radosław
dc.contributor.authorBurt, Deborah J
dc.contributor.authorSimpson, Kathryn L
dc.contributor.authorMorris, Karen
dc.contributor.authorPepper, Stuart D
dc.contributor.authorNonaka, Daisuke
dc.contributor.authorGreystoke, Alastair
dc.contributor.authorKelly, Paul
dc.contributor.authorBola, Becky
dc.contributor.authorKrebs, Matthew G
dc.contributor.authorAntonello, Jenny
dc.contributor.authorAyub, Mahmood
dc.contributor.authorFaulkner, Suzanne
dc.contributor.authorPriest, Lynsey
dc.contributor.authorCarter, Louise
dc.contributor.authorTate, Catriona
dc.contributor.authorMiller, Crispin J
dc.contributor.authorBlackhall, Fiona H
dc.contributor.authorBrady, Ged
dc.contributor.authorDive, Caroline
dc.date.accessioned2014-06-18T14:12:03Z
dc.date.available2014-06-18T14:12:03Z
dc.date.issued2014-06-01
dc.identifier.citationTumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. 2014: Nat Meden
dc.identifier.issn1546-170X
dc.identifier.pmid24880617
dc.identifier.doi10.1038/nm.3600
dc.identifier.urihttp://hdl.handle.net/10541/321831
dc.description.abstractSmall-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.
dc.languageENG
dc.language.isoenen
dc.rightsArchived with thanks to Nature medicineen
dc.titleTumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentClinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.en
dc.identifier.journalNature Medicineen
html.description.abstractSmall-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.


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