Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Br J Cancer. 2022 Aug;127(3):569-576. doi: 10.1038/s41416-022-01811-9. Epub 2022 Apr 19.
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.
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.
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.
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.
小细胞肺癌（SCLC）是一种侵袭性恶性肿瘤，目前尚无明确的生物标志物。SLFN11 是一种 DNA/RNA 解旋酶，可使癌细胞对 DNA 损伤剂敏感，已成为包括铂类和 PARP 抑制剂在内的多种药物类别的有前途的预测生物标志物。在循环肿瘤细胞（CTC）中检测 SLFN11 可能为组织取样提供有价值的替代方法。
评估肿瘤样本中的 SLFN11 表达，并对循环肿瘤细胞（CTC）进行纵向特征分析，以确定其作为反应生物标志物的潜在作用。
在 196 例 SCLC 肿瘤中，免疫组化（IHC）显示 51%表达 SLFN11。此外，29 例胸外高级神经内分泌肿瘤中有 20 例表达 SLFN11。在 42 例 SCLC 患者的 64 份血液样本中，83%（53/64）的样本可检测到 CTC，55%（29/53）的样本中检测到 SLFN11 阳性 CTC。正在接受铂类治疗的患者的 CTC 数量最低，SLFN11 阳性 CTC 的比例也最低（p=0.014）。来自具有纵向样本的患者的分析表明，CTC 数量和 SLFN11 表达减少与临床反应相关。
使用非侵入性液体活检可在 SCLC 患者的 CTC 中监测 SLFN11 水平。能够在 SCLC 患者的 CTC 中检测到 SLFN11 增加了一种有价值的工具，用于检测和纵向监测这种有前途的生物标志物。
