Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 expression, with limited targeted therapies and poor outcomes. Epigenetic dysregulation, particularly aberrant DNA methylation, is a key driver. Decitabine, a DNA methyltransferase inhibitor (DNMTi), shows promise by reactivating silenced tumor suppressor genes and modulating immune responses. This systematic review evaluates preclinical and clinical evidence on decitabine’s efficacy, mechanisms, and translational potential in TNBC.Methods: A PRISMA-2020 compliant search of PubMed, EBSCO, Web of Science, and Semantic Scholar was conducted up to April 2025. Included studies assessed decitabine alone or in combination in TNBC preclinical or clinical settings. Risk of bias was assessed using QUIPS and RoB 2.0 tools.Results: Twenty-five studies were included. In vitro, decitabine-induced growth inhibition, apoptosis, and re-expression of silenced genes (such asBRCA1andCDH1). In vivo, it reduced tumor burden and enhanced anti-tumor immunity through MHC-I, PD-L1, and STING pathway upregulation. Synergy was noted with anti-PD-1, HDAC inhibitors, and chemotherapy. Resistance mechanisms included persistent DNMT activity, low DCK, and miRNA-driven escape (miR-155–TSPAN5).Conclusions: Decitabine demonstrates strong preclinical and early clinical potential in TNBC via epigenetic reprogramming and immune activation. Future strategies should focus on biomarker-based selection and resistance mitigation.
**背景/目的**：三阴性乳腺癌（TNBC）是一种侵袭性亚型，缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）的表达，靶向治疗手段有限且预后不良。表观遗传失调，特别是异常的DNA甲基化，是其关键驱动因素。地西他滨作为一种DNA甲基转移酶抑制剂（DNMTi），通过重新激活沉默的肿瘤抑制基因和调节免疫反应而显示出治疗潜力。本系统综述旨在评估地西他滨在TNBC中的疗效、作用机制及转化潜力的临床前与临床证据。 **方法**：遵循PRISMA-2020指南，系统检索了截至2025年4月的PubMed、EBSCO、Web of Science和Semantic Scholar数据库。纳入的研究评估了地西他滨单药或联合用药在TNBC临床前或临床环境中的应用。使用QUIPS和RoB 2.0工具评估偏倚风险。 **结果**：共纳入25项研究。体外实验表明，地西他滨能诱导生长抑制、细胞凋亡，并重新激活沉默基因（如BRCA1和CDH1）的表达。体内实验显示，它能通过上调MHC-I、PD-L1和STING通路来降低肿瘤负荷并增强抗肿瘤免疫。研究观察到其与抗PD-1抗体、组蛋白去乙酰化酶抑制剂及化疗药物具有协同作用。耐药机制包括持续的DNMT活性、低水平的脱氧胞苷激酶以及miRNA驱动的逃逸机制（如miR-155–TSPAN5通路）。 **结论**：地西他滨通过表观遗传重编程和免疫激活，在TNBC中展现出强大的临床前及早期临床潜力。未来的策略应侧重于基于生物标志物的患者选择和耐药性克服。
肿瘤(癌症)患者之家