Faculty, Staff and Student Publications

Publication Date

8-1-2022

Journal

British Journal of Cancer

Abstract

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.

Keywords

Biomarkers, Biomarkers, Tumor, Cell Line, Tumor, DNA, Humans, Lung Neoplasms, Neoplastic Cells, Circulating, Nuclear Proteins, Platinum, Small Cell Lung Carcinoma, Small-cell lung cancer, Predictive markers

DOI

10.1038/s41416-022-01811-9

PMID

35440668

PMCID

PMC9346119

PubMedCentral® Posted Date

4-19-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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