Journal
BRITISH JOURNAL OF CANCER
Volume 127, Issue 3, Pages 569-576Publisher
SPRINGERNATURE
DOI: 10.1038/s41416-022-01811-9
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Funding
- NIH [T32 CA009666, R01-CA207295]
- NIH/NCI [U01-CA213273, R50-CA243698]
- University of Texas-Southwestern and MD Anderson Lung SPORE [5 P50 CA070907]
- University of Texas MD Anderson Lung Cancer Moon Shot Program
- Andrew Sabin Family Fellowship
- Abell Hangar Foundation
- LUNGevity Foundation Career Development Award
- Rexanna Foundation for Fighting Lung Cancer
- CPRIT Early Clinical Investigator Award
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SLFN11 can serve as a potential biomarker for SCLC and can be detected in CTCs. Monitoring SLFN11 in CTCs may provide a valuable tool for the detection and longitudinal monitoring of this biomarker.
Introduction 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. Methods 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. Results 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. Conclusions 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.
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