小细胞肺癌（SCLC）的特点是预后不佳。迄今为止，为了识别 SCLC 患者个性化治疗的新型生物标志物，已经做出了许多努力。 Schlafen 11 (SLFN11) 是一种在许多癌症中以不同方式表达的蛋白质，最近成为一种新的潜在生物标志物。 SLFN11 的较低表达与 SCLC 和其他肿瘤的较差预后相关。 SLFN11 在肿瘤发生中发挥作用，在 DNA 损伤的情况下通过阻断复制叉诱导复制停滞。 SLFN11 还与染色质可及性、蛋白毒性应激和雷帕霉素信号通路的哺乳动物靶标相互作用。 SLFN11 的表达受到表观遗传机制的调节，包括启动子甲基化、组蛋白脱乙酰化和组蛋白甲基化。 SLFN11 的下调与不同癌症类型中对拓扑异构酶 I 和 II 抑制剂、烷化剂和聚 ADP-核糖聚合酶抑制剂的较差反应相关。一些探索克服 SLFN11 水平低的肿瘤耐药性的策略的研究显示出有希望的结果。其中一种策略包括与共济失调毛细血管扩张和 Rad3 相关通路相互作用，在低水平 SLFN11 存在的情况下，组成型激活并导致细胞存活和肿瘤生长。此外，SLFN11 的表达随时间变化是动态的，不同的抗癌治疗和液体活检似乎是捕获 SLFN11 不同表达的有吸引力的工具。尽管如此，仍需要进一步研究探索 SLFN11 作为预测生物标志物、其纵向变化以及克服耐药性的新策略。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Small cell lung cancer (SCLC) is characterized by a dismal prognosis. Many efforts have been made so far for identifying novel biomarkers for a personalized treatment for SCLC patients. Schlafen 11 (SLFN11) is a protein differently expressed in many cancers and recently emerged as a new potential biomarker. Lower expression of SLFN11 correlates with a worse prognosis in SCLC and other tumors. SLFN11 has a role in tumorigenesis, inducing replication arrest in the presence of DNA damage through the block of the replication fork. SLFN11 interacts also with chromatin accessibility, proteotoxic stress and mammalian target of rapamycin signalling pathway. The expression of SLFN11 is regulated by epigenetic mechanisms, including promoter methylation, histone deacetylation, and the histone methylation. The downregulation of SLFN11 correlates with a worse response to topoisomerase I and II inhibitors, alkylating agents, and poly ADP-ribose polymerase inhibitors in different cancer types. Some studies exploring strategies for overcoming drug resistance in tumors with low levels of SLFN11 showed promising results. One of these strategies includes the interaction with the Ataxia Telangiectasia and Rad3-related pathway, constitutively activated and leading to cell survival and tumor growth in the presence of low levels of SLFN11. Furthermore, the expression of SLFN11 is dynamic through time and different anticancer therapy and liquid biopsy seems to be an attractive tool for catching SLFN11 different expressions. Despite this, further investigations exploring SLFN11 as a predictive biomarker, its longitudinal changes, and new strategies to overcome drug resistances are needed.Copyright © 2024 Elsevier Ltd. All rights reserved.