Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer
Autor: | Stuart D Pepper, Cassandra L Hodgkinson, Deborah J. Burt, Daisuke Nonaka, Fiona H Blackhall, Paul P. Kelly, Francesca Trapani, Mahmood Ayub, Crispin J. Miller, Lynsey Priest, Robert Metcalf, Radoslaw Polanski, Alastair Greystoke, Matthew G Krebs, Karen Morris, Caroline Dive, Jenny Antonello, Suzanne Faulkner, Christopher J. Morrow, Becky Bola, Ged Brady, Yaoyong Li, Louise Carter, Dominic G. Rothwell, Catriona Tate, Kathryn Simpson |
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Rok vydání: | 2014 |
Předmět: |
Pathology
medicine.medical_specialty Lung Neoplasms medicine.medical_treatment Molecular Sequence Data Transplantation Heterologous Heterologous Drug resistance General Biochemistry Genetics and Molecular Biology Mice Circulating tumor cell Mice Inbred NOD medicine Biomarkers Tumor Animals Humans Neoplasm Metastasis Lung cancer Chemotherapy business.industry fungi food and beverages General Medicine medicine.disease Neoplastic Cells Circulating Small Cell Lung Carcinoma Transplantation Disease Models Animal Cell Transformation Neoplastic Treatment Outcome DNA profiling Drug Resistance Neoplasm Female business Neoplasm Transplantation Explant culture |
Zdroj: | Nature medicine. 20(8) |
ISSN: | 1546-170X |
Popis: | 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. |
Databáze: | OpenAIRE |
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