Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer

Br J Cancer. 2022 Aug;127(3):569-576. doi: 10.1038/s41416-022-01811-9. Epub 2022 Apr 19.

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.

MeSH terms

  • Biomarkers
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • DNA / therapeutic use
  • Humans
  • Lung Neoplasms* / drug therapy
  • Neoplastic Cells, Circulating* / pathology
  • Nuclear Proteins* / genetics
  • Platinum / therapeutic use
  • Small Cell Lung Carcinoma* / drug therapy

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • Nuclear Proteins
  • SLFN11 protein, human
  • Platinum
  • DNA