DNA-damaging agents exploit increased genomic instability, a hallmark of cancer. Recently, inhibitors targeting the DNA damage response (DDR) pathways, such as PARP inhibitors, have also shown promising therapeutic potential. However, not all tumors respond well to these treatments, suggesting additional determinants of response are required. Schlafen 11 (SLFN11), a putative DNA/RNA helicase that induces irreversible replication block, is emerging as an important regulator of cellular response to DNA damage. Preclinical and emerging clinical trial data suggest that SLFN11 is a predictive biomarker of response to a wide range of therapeutics that cause DNA damage including platinum salts and topoisomerase I/II inhibitors, as well as PARP inhibitors, which has raised exciting possibilities for its clinical application. In this article, we review the function, prevalence, and clinical testing of SLFN11 in tumor biopsy samples and circulating tumor cells. We discuss mounting evidence of SLFN11 as a key predictive biomarker for a wide range of cancer therapeutics and as a prognostic marker across several cancer types. Furthermore, we discuss emerging areas of investigation such as epigenetic reactivation of SLFN11 and its role in activating immune response. We then provide perspectives on open questions and future directions in studying this important biomarker.

DNA 损伤剂利用增加的基因组不稳定性，这是癌症的标志。最近，针对 DNA 损伤反应 (DDR) 通路的抑制剂，如 PARP 抑制剂，也显示出有希望的治疗潜力。然而，并不是所有的肿瘤都对这些治疗反应良好，这表明需要额外的反应决定因素。Schlafen 11 (SLFN11) 是一种假定的 DNA/RNA 解旋酶，可诱导不可逆的复制阻滞，正在成为细胞对 DNA 损伤反应的重要调节因子。临床前和新出现的临床试验数据表明，SLFN11 是一种预测性生物标志物，可预测对导致 DNA 损伤的多种疗法的反应，包括铂盐和拓扑异构酶 I/II 抑制剂，以及 PARP 抑制剂，这为其临床应用带来了令人兴奋的可能性. 在本文中，我们回顾了 SLFN11 在肿瘤活检样本和循环肿瘤细胞中的功能、流行率和临床测试。我们讨论越来越多的证据表明 SLFN11 作为广泛癌症治疗的关键预测生物标志物和作为多种癌症类型的预后标志物。此外，我们讨论了新兴的研究领域，例如 SLFN11 的表观遗传再激活及其在激活免疫反应中的作用。然后，我们就研究这一重要生物标志物的开放性问题和未来方向提供了观点。我们讨论新兴的研究领域，例如 SLFN11 的表观遗传再激活及其在激活免疫反应中的作用。然后，我们就研究这一重要生物标志物的开放性问题和未来方向提供了观点。我们讨论新兴的研究领域，例如 SLFN11 的表观遗传再激活及其在激活免疫反应中的作用。然后，我们就研究这一重要生物标志物的开放性问题和未来方向提供了观点。