癌症头颈部的DNA修复、表观遗传失调和细胞因子网络串扰：新的治疗机会和临床试验
DNA Repair, Epigenetic Dysregulation, and Cytokine Network Crosstalk in Head and Neck Cancer: Emerging Therapeutic Opportunities and Clinical Trials.
摘要(中文译文)
头颈癌（HNC）以显著的基因组不稳定性、治疗耐药及欠佳的生存结局为特征，尤其在晚期疾病中更为突出。本综述旨在批判性地审视DNA损伤应答（DDR）通路、表观遗传失调与细胞因子驱动的炎症网络之间的机制性相互作用，并评估其对HNC进展及治疗脆弱性的综合影响。近期研究表明，DDR通路缺陷促进基因组不稳定性，并通过cGAS-STING通路激活胞质DNA感知，导致I型干扰素产生及肿瘤微环境调控。此外，表观遗传改变影响DNA修复机制和免疫应答。涉及IL-6、TNF-α及NF-κB/STAT3信号的细胞因子网络在肿瘤进展、免疫逃逸和治疗耐药中发挥核心作用。联合治疗策略，包括PARP/ATR抑制剂联合免疫检查点阻断及细胞因子靶向药物，在临床前及早期临床研究中显示出良好前景。DDR缺陷、表观遗传改变与炎症信号之间复杂的交互作用构成了HNC病理生物学及治疗耐药的核心轴。通过合理的联合策略靶向这些相互关联的通路，为增强治疗效果和推进精准肿瘤学提供了有前景的途径。持续整合分子谱分析与生物标志物驱动的方法对于优化患者分层和改善HNC临床结局至关重要。
Abstract
Head and neck cancer (HNC) is characterized by profound genomic instability, therapeutic resistance, and suboptimal survival outcomes, particularly in advanced-stage disease. This review aims to critically examine the mechanistic interplay between DNA damage response (DDR) pathways, epigenetic dysregulation, and cytokine-driven inflammatory networks, and to evaluate their collective impact on HNC progression and therapeutic vulnerability. Recent studies have demonstrated that defects in DDR pathways contribute to genomic instability and activate cytosolic DNA sensing via the cGAS-STING pathway, leading to type I interferon production and modulation of the tumor microenvironment. In addition, epigenetic alterations influence DNA repair mechanisms and immune responses. Cytokine networks involving IL-6, TNF-α, and NF-κB/STAT3 signaling play a central role in tumor progression, immune evasion, and therapy resistance. Combination therapies, including PARP/ATR inhibitors with immune checkpoint blockade and cytokine-targeting agents, have shown promising results in preclinical and early clinical studies. The intricate crosstalk among DDR deficiency, epigenetic alterations, and inflammatory signaling constitutes a central axis in HNC pathobiology and therapeutic resistance. Targeting these interconnected pathways through rational combination strategies offers a promising avenue to enhance treatment efficacy and advance precision oncology. Continued integration of molecular profiling and biomarker-driven approaches will be essential to optimize patient stratification and improve clinical outcomes in HNC.
如何引用
AMA
Nistha Agarwal, Garima Sharma, Ashish Ranjan Sharma, Vinod Kumar Gupta, Yuyuan Guo, Abhimanyu Kumar Jha, et al. DNA Repair, Epigenetic Dysregulation, and Cytokine Network Crosstalk in Head and Neck Cancer: Emerging Therapeutic Opportunities and Clinical Trials.. Current oncology reports. 2026; doi:10.1007/s11912-026-01808-0.
APA
Nistha Agarwal, Garima Sharma, Ashish Ranjan Sharma, Vinod Kumar Gupta, Yuyuan Guo, Abhimanyu Kumar Jha, et al (2026). DNA Repair, Epigenetic Dysregulation, and Cytokine Network Crosstalk in Head and Neck Cancer: Emerging Therapeutic Opportunities and Clinical Trials.. Current oncology reports. https://doi.org/10.1007/s11912-026-01808-0
GB/T 7714
Nistha Agarwal, Garima Sharma, Ashish Ranjan Sharma, Vinod Kumar Gupta, Yuyuan Guo, Abhimanyu Kumar Jha, et al. DNA Repair, Epigenetic Dysregulation, and Cytokine Network Crosstalk in Head and Neck Cancer: Emerging Therapeutic Opportunities and Clinical Trials.[J]. Current oncology reports, 2026 doi:10.1007/s11912-026-01808-0.
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