期刊
NATURE MEDICINE
卷 20, 期 8, 页码 897-903出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3600
关键词
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资金
- Cancer Research UK [C5759/A12328]
- Manchester Experimental Cancer Medicine Centre [C1467/A15578]
- Manchester Cancer Research Centre [A12197]
- European Union CHEMORES [LSHG-CT-2007-037665]
- AstraZeneca
- Academy of Medical Sciences (AMS) [AMS-SGCL7-Krebs] Funding Source: researchfish
- Cancer Research UK [15675, 19278] Funding Source: researchfish
- National Institute for Health Research [CL-2011-06-002] Funding Source: researchfish
Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor with early dissemination and dismal prognosis, accounts for 15-20% of lung cancer cases and similar to 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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