Plasticity of circulating tumor cells in small cell lung cancer

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with low five-year survival rates. Recently described molecular phenotypes of SCLC exhibit differential vulnerabilities heralding potential for stratified treatment. Whilst tumor biopsy in SCLC is challenging, circulating tumor cell...

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Bibliographic Details
Published in:Scientific reports 2023-07, Vol.13 (1), p.11775-11, Article 11775
Main Authors: Seo, Jiyoun, Kumar, Mihir, Mason, Jeremy, Blackhall, Fiona, Matsumoto, Nicholas, Dive, Caroline, Hicks, James, Kuhn, Peter, Shishido, Stephanie N.
Format: Article
Language:English
Subjects:
631/80/304
692/4028/67/1612/2143
Aggression
Biopsy
Clinical trials
Genomic analysis
Heterogeneity
Humanities and Social Sciences
Humans
Lung cancer
Lung Neoplasms - genetics
multidisciplinary
Neoplastic Cells, Circulating
Neuroendocrine Tumors
Patients
Phenotypes
Phenotypic plasticity
Plasticity
Science
Science (multidisciplinary)
Small cell lung carcinoma
Small Cell Lung Carcinoma - genetics
Survival
Therapeutic targets
Tumor cells
Tumors
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Summary:Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with low five-year survival rates. Recently described molecular phenotypes of SCLC exhibit differential vulnerabilities heralding potential for stratified treatment. Whilst tumor biopsy in SCLC is challenging, circulating tumor cells in the liquid biopsy are prevalent and can be repeatedly sampled accommodating the dynamic plasticity of SCLC phenotypes. The aim of this study was to characterize the heterogeneity of rare circulating cells with confirmed tumor origin and to explore a liquid biopsy approach for future clinical trials of targeted therapies. This study applied the 3rd generation of a previously validated direct imaging platform to 14 chemo-naive SCLC patients and 10 non-cancerous normal donor (ND) samples. Phenotypic heterogeneity of circulating rare cells in SCLC was observed and a patient-level classification model was established to stratify SCLC patients from non-cancerous donors. Eight rare cell groups, with combinations of epithelial, endothelial, and mesenchymal biomarker expression patterns, were phenotypically characterized. The single-cell genomic analysis confirmed the cancer cell plasticity in every rare cell group harboring clonal genomic alterations. This study shows rare cell heterogeneity and confirms cellular plasticity in SCLC providing a valuable resource for better opportunities to discover novel therapeutic targets in SCLC.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-38881-5