循环游离EB病毒DNA检测用于鼻咽癌：迈向ctDNA指导的风险适应性个体化治疗

文献信息

中文摘要

循环肿瘤来源DNA（ctDNA）已成为癌症筛查、治疗前预后风险分层、治疗中反应评估和治疗后复发监测的关键工具。寻找肿瘤特异性ctDNA生物标志物一直是癌症研究中长期而协同的努力。其中，游离EB病毒（EBV）DNA（cfEBV DNA）已被认为是流行地区鼻咽癌（NPC）的稳健疾病特异性生物标志物。EBV是第一个与人类恶性肿瘤相关的DNA病毒，在NPC中主要以潜伏形式存在。对于NPC患者，死亡肿瘤细胞释放的cfEBV DNA不仅反映肿瘤负荷，还与宿主免疫状态和病毒清除能力相关。更重要的是，化疗和放疗等外部应激因素可将EBV感染状态从潜伏期转变为裂解期，这可能导致病毒DNA合成增加以及裂解相关蛋白的表达。这些治疗诱导的变化反过来可能影响NPC的治疗疗效。由于这些独特特性，cfEBV DNA成为纵向评估NPC治疗反应和临床结局的有前景的生物标志物。本综述总结了cfEBV DNA在疾病筛查、预后判断和监测中应用的最新进展，特别强调其在治疗期间的连续追踪，用于实时反应评估和动态复发风险监测。我们还讨论了在治疗期间通过纵向cfEBV DNA监测指导NPC风险适应性个体化治疗策略的未来前景。

英文摘要

Circulating tumor-derived DNA (ctDNA) has emerged as a pivotal tool for cancer screening, pre-treatment prognostic risk stratification, on-treatment response evaluation, and post-treatment recurrence surveillance. The pursuit of tumor-specific ctDNA biomarkers has been a long-standing and concerted effort in cancer research. Among these, cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA) has been recognized as a robust disease-specific biomarker for nasopharyngeal carcinoma (NPC) in endemic regions. EBV was the first DNA virus linked to human malignancies and is predominantly present in its latent form in NPC. For patients with NPC, cfEBV DNA released by dead tumor cells not only reflects tumor burden but is also associated with the host immune status and viral clearance capacity. More importantly, external stressors such as chemotherapy and radiotherapy can alter the infection status of EBV from latency to lytic phase, which may lead to increased viral DNA synthesis, as well as the expression of lytic-associated proteins. These treatment-induced changes can, in turn, impact the therapeutic efficacy of NPC. Owing to these unique properties, cfEBV DNA emerges as a promising biomarker for the longitudinal assessment of therapeutic response and clinical outcomes in NPC. This review summarizes recent advances in the application of cfEBV DNA for disease screening, prognostication, and surveillance, with particular emphasis on its serial tracing during treatment for real-time response evaluation and dynamic recurrence risk monitoring. We also discuss future perspectives on risk-adaptive, individualized treatment strategies of NPC guided by longitudinal cfEBV DNA monitoring during treatment.