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

Cassandra L. Hodgkinson | Zendy; Christopher J. Morrow | Zendy; Yaoyong Li | Zendy; Robert Metcalf | Zendy; Dominic G. Rothwell | Zendy; Francesca Trapani | Zendy; Radosław Polański | Zendy; Deborah J. Burt | Zendy; Kathryn Simpson | Zendy; Karen Morris | Zendy; Stuart D Pepper | Zendy; Daisuke aka | Zendy; Alastair Greystoke | Zendy; Paul A. Kelly | Zendy; Becky M. Bola | Zendy; Matthew Krebs | Zendy; Jenny Antonello | Zendy; Mahmood Ayub | Zendy; Suzanne Faulkner | Zendy; Lynsey Priest | Zendy; Louise Carter | Zendy; Catriona Tate | Zendy; Crispin Miller | Zendy; Fiona Blackhall | Zendy; Ged Brady | Zendy; Caroline Dive | Zendy

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

Author(s) -

Cassandra L. Hodgkinson,

Christopher J. Morrow,

Yaoyong Li,

Robert Metcalf,

Dominic G. Rothwell,

Francesca Trapani,

Radosław Polański,

Deborah J. Burt,

Kathryn Simpson,

Karen Morris,

Stuart D Pepper,

Daisuke aka,

Alastair Greystoke,

Paul A. Kelly,

Becky M. Bola,

Matthew Krebs,

Jenny Antonello,

Mahmood Ayub,

Suzanne Faulkner,

Lynsey Priest,

Louise Carter,

Catriona Tate,

Crispin Miller,

Fiona Blackhall,

Ged Brady,

Caroline Dive

Publication year - 2014

Publication title -

nature medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 19.536

H-Index - 547

eISSN - 1546-170X

pISSN - 1078-8956

DOI - 10.1038/nm.3600

Subject(s) - circulating tumor cell , etoposide , lung cancer , liquid biopsy , medicine , chemotherapy , cancer research , precision medicine , personalized medicine , drug resistance , oncology , cancer , pathology , biology , bioinformatics , microbiology and biotechnology , metastasis

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.

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