Feng Yue, Li Yingze, Zhang Zhenhao, Dai Yuxuan, Gou Xingchun, Lao Kejing, Zhang Running
School of Clinical Medicine, Shaanxi University of Chinese Medicine, No.1 Century Road, Qindu District, Xianyang, 712046, China.
Shaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi'an Medical University, No.1 Xinwang Road, Xi'an, 710021, China.
Cancer Chemother Pharmacol. 2025 Jun 18;95(1):60. doi: 10.1007/s00280-025-04781-w.
SLFN11, a DNA/RNA helicase implicated in replication stress response, has recently emerged as a pivotal determinant of chemotherapy sensitivity across multiple cancer types. The expression level of SLFN11 in various cancers is significantly positively correlated with the sensitivity of cancer cell DNA damage agents. SLFN11 exerts its chemosensitizing effects by RPA-coated single-stranded DNA (ssDNA) at stressed replication forks at stalled replication forks, thereby potentiating the cytotoxicity of platinum agents, topoisomerase inhibitors, and PARP inhibitors. Its roles in inhibiting ATR translation, mediating p53-independent apoptosis, sensitizing towards IFN-γ and enhancing chromatin accessibility also remain investigational. The down-regulation of SLFN11 expression is associated with epigenetic silencing including promoter methylation, histone deacetylation, and the histone methylation. In this paper, we reviewed the recent progress of SLFN11 as predictive biomarker and therapeutic target in multiple cancers including medulloblastoma, prostate cancer, breast cancer, ovarian cancer, lung cancer, head and neck cancer, esophageal carcinoma, gastric carcinoma and colorectal cancer. We also summarized 10 active clinical trials conducting molecular analyses to assess SLFN11's role. By bridging mechanistic understanding with translational opportunities, this review provides a roadmap for leveraging SLFN11 to overcome chemoresistance and advance precision oncology.
SLFN11是一种参与复制应激反应的DNA/RNA解旋酶，最近已成为多种癌症化疗敏感性的关键决定因素。SLFN11在各种癌症中的表达水平与癌细胞DNA损伤剂的敏感性显著正相关。SLFN11通过在停滞复制叉处被RPA包被的单链DNA（ssDNA）发挥其化学增敏作用，从而增强铂类药物、拓扑异构酶抑制剂和PARP抑制剂的细胞毒性。其在抑制ATR翻译、介导非p53依赖性凋亡、对IFN-γ敏感和增强染色质可及性方面的作用仍在研究中。SLFN11表达的下调与包括启动子甲基化、组蛋白去乙酰化和组蛋白甲基化在内的表观遗传沉默有关。在本文中，我们综述了SLFN11作为多种癌症（包括髓母细胞瘤、前列腺癌、乳腺癌、卵巢癌、肺癌、头颈癌、食管癌、胃癌和结直肠癌）的预测生物标志物和治疗靶点的最新进展。我们还总结了10项正在进行的评估SLFN11作用的分子分析的活性临床试验。通过将机制理解与转化机会联系起来，本综述为利用SLFN11克服化疗耐药性和推进精准肿瘤学提供了路线图。
