Details

Autor(en) / Beteiligte

• Hodgkinson, Cassandra L
• Morrow, Christopher J
• Li, Yaoyong
• Metcalf, Robert L
• Rothwell, Dominic G
• Trapani, Francesca
• Polanski, Radoslaw
• 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
• Brady, Ged
• Dive, Caroline

Titel

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

Ist Teil von

• Nature medicine, 2014-08, Vol.20 (8), p.897-903

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Circulating tumor cells from patients with small-cell lung cancer can form tumors in mice, and their derived explants recapitulate the patients' response to chemotherapy. 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.