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- Title
Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer.
- Authors
Zhang, Bingnan; Stewart, C. Allison; Wang, Qi; Cardnell, Robert J.; Rocha, Pedro; Fujimoto, Junya; Solis Soto, Luisa M.; Wang, Runsheng; Novegil, Veronica; Ansell, Peter; He, Lei; Fernandez, Luisa; Jendrisak, Adam; Gilbertson, Cole; Schonhoft, Joseph D.; Byun, Jiyun; Jones, Joshua; Anderson, Amanda K. L.; Aparicio, Ana; Tran, Hai
- Abstract
<bold>Introduction: </bold>Small cell lung cancer (SCLC) is an aggressive malignancy with no established biomarkers. Schlafen 11(SLFN11), a DNA/RNA helicase that sensitises cancer cells to DNA-damaging agents, has emerged as a promising predictive biomarker for several drug classes including platinum and PARP inhibitors. Detection of SLFN11 in circulating tumour cells (CTCs) may provide a valuable alternative to tissue sampling.<bold>Methods: </bold>SLFN11 expression was evaluated in tumour samples and characterised in circulating tumour cells (CTC) longitudinally to determine its potential role as a biomarker of response.<bold>Results: </bold>Among 196 SCLC tumours, 51% expressed SLFN11 by IHC. In addition, 20/29 extra-thoracic high-grade neuroendocrine tumours expressed SLFN11 expression. In 64 blood samples from 42 SCLC patients, 83% (53/64) of samples had detectable CTCs, and SLFN11-positive CTCs were detected in 55% (29/53). Patients actively receiving platinum treatment had the lowest number of CTCs and a lower percentage of SLFN11-positive CTCs (p = 0.014). Analysis from patients with longitudinal samples suggest a decrease in CTC number and in SLFN11 expression that correlates with clinical response.<bold>Conclusions: </bold>SLFN11 levels can be monitored in CTCs from SCLC patients using non-invasive liquid biopsies. The ability to detect SLFN11 in CTCs from SCLC patients adds a valuable tool for the detection and longitudinal monitoring of this promising biomarker.
- Subjects
LUNG cancer; DNA; NUCLEAR proteins; LUNG tumors; METASTASIS; PLATINUM; RESEARCH funding; CELL lines
- Publication
British Journal of Cancer, 2022, Vol 127, Issue 3, p569
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-022-01811-9