SLFN11: a pan-cancer biomarker for DNA-targeted drugs sensitivity and therapeutic strategy guidance

Therapeutic responses to identical chemotherapy regimens often vary significantly among patients with the same type of cancer, underscoring the need for additional biomarkers to identify individuals most likely to benefit from specific treatments. The expression of SLFN11 (Schlafen11) has been ident...

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Main Authors: Kunzhong Zhou, Yuewen Li, Weifang Wang, Yilin Chen, Bingyan Qian, Yiteng Liang, Hongmei Li, Ruiting Xu, Li Zhuang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1582738/full
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author Kunzhong Zhou
Yuewen Li
Weifang Wang
Yilin Chen
Bingyan Qian
Yiteng Liang
Hongmei Li
Ruiting Xu
Li Zhuang
author_facet Kunzhong Zhou
Yuewen Li
Weifang Wang
Yilin Chen
Bingyan Qian
Yiteng Liang
Hongmei Li
Ruiting Xu
Li Zhuang
author_sort Kunzhong Zhou
collection DOAJ
description Therapeutic responses to identical chemotherapy regimens often vary significantly among patients with the same type of cancer, underscoring the need for additional biomarkers to identify individuals most likely to benefit from specific treatments. The expression of SLFN11 (Schlafen11) has been identified as a potential biomarker for predicting patient responses to DNA-damaging agents and PARP inhibitors, as it irreversibly blocks DNA replication under replication stress, thereby increasing the sensitivity of cancer cells to various DNA-damaging agents and PARP inhibitors. Preclinical and clinical trial data suggest that SLFN11 can predict therapeutic responses to multiple DNA- targeted drugs, including platinum-based agents, topoisomerase I/II inhibitors, DNA synthesis inhibitors, and PARP inhibitors. Leveraging the expression status of SLFN11 or modulating its expression offers exciting possibilities for clinical applications. In this review, we summarize the structure and function of SLFN11, as well as its progress as a biomarker across various cancer types. We also review the regulation of SLFN11 expression, its dynamic expression patterns, and potential strategies for combination therapies to enhance efficacy based on SLFN11 status. Furthermore, we discuss the potential of SLFN11 expression status in overcoming resistance to DNA-damaging drugs, optimizing treatment strategies, and advancing precision cancer therapy.
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publishDate 2025-07-01
publisher Frontiers Media S.A.
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series Frontiers in Oncology
spelling doaj-art-6d13e84bb74c4ac89596756a3003ef622025-08-20T02:50:32ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.15827381582738SLFN11: a pan-cancer biomarker for DNA-targeted drugs sensitivity and therapeutic strategy guidanceKunzhong ZhouYuewen LiWeifang WangYilin ChenBingyan QianYiteng LiangHongmei LiRuiting XuLi ZhuangTherapeutic responses to identical chemotherapy regimens often vary significantly among patients with the same type of cancer, underscoring the need for additional biomarkers to identify individuals most likely to benefit from specific treatments. The expression of SLFN11 (Schlafen11) has been identified as a potential biomarker for predicting patient responses to DNA-damaging agents and PARP inhibitors, as it irreversibly blocks DNA replication under replication stress, thereby increasing the sensitivity of cancer cells to various DNA-damaging agents and PARP inhibitors. Preclinical and clinical trial data suggest that SLFN11 can predict therapeutic responses to multiple DNA- targeted drugs, including platinum-based agents, topoisomerase I/II inhibitors, DNA synthesis inhibitors, and PARP inhibitors. Leveraging the expression status of SLFN11 or modulating its expression offers exciting possibilities for clinical applications. In this review, we summarize the structure and function of SLFN11, as well as its progress as a biomarker across various cancer types. We also review the regulation of SLFN11 expression, its dynamic expression patterns, and potential strategies for combination therapies to enhance efficacy based on SLFN11 status. Furthermore, we discuss the potential of SLFN11 expression status in overcoming resistance to DNA-damaging drugs, optimizing treatment strategies, and advancing precision cancer therapy.https://www.frontiersin.org/articles/10.3389/fonc.2025.1582738/fullSchlafen11 (SLFN11)DNA damaging agentsPARP inhibitorspan-cancerDNA damage repair mechanismsepigenetics
spellingShingle Kunzhong Zhou
Yuewen Li
Weifang Wang
Yilin Chen
Bingyan Qian
Yiteng Liang
Hongmei Li
Ruiting Xu
Li Zhuang
SLFN11: a pan-cancer biomarker for DNA-targeted drugs sensitivity and therapeutic strategy guidance
Frontiers in Oncology
Schlafen11 (SLFN11)
DNA damaging agents
PARP inhibitors
pan-cancer
DNA damage repair mechanisms
epigenetics
title SLFN11: a pan-cancer biomarker for DNA-targeted drugs sensitivity and therapeutic strategy guidance
title_full SLFN11: a pan-cancer biomarker for DNA-targeted drugs sensitivity and therapeutic strategy guidance
title_fullStr SLFN11: a pan-cancer biomarker for DNA-targeted drugs sensitivity and therapeutic strategy guidance
title_full_unstemmed SLFN11: a pan-cancer biomarker for DNA-targeted drugs sensitivity and therapeutic strategy guidance
title_short SLFN11: a pan-cancer biomarker for DNA-targeted drugs sensitivity and therapeutic strategy guidance
title_sort slfn11 a pan cancer biomarker for dna targeted drugs sensitivity and therapeutic strategy guidance
topic Schlafen11 (SLFN11)
DNA damaging agents
PARP inhibitors
pan-cancer
DNA damage repair mechanisms
epigenetics
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1582738/full
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