Nasopharyngeal carcinoma (NPC) is a malignancy endemic to East Asia and is caused by Epstein-Barr Virus (EBV)-mediated cancerous transformation of epithelial cells. The standard of care treatment for NPC involves radiation and chemotherapy. While treatment outcomes continue to improve, up to 50% of patients can be expected to recur by five years, and additional innovative treatment options are needed. We posit that a potential way to do this is by targeting the underlying cause of malignant transformation, namely EBV. One method by which EBV escapes immune surveillance is by undergoing latent phase replication, during which EBV expression of immunogenic proteins is reduced. However, chemoradiation is known to drive conversion of EBV from a latent to a lytic phase. This creates an opportunity for the targeting of EBV-infected cells utilizing anti-viral drugs. Indeed, we found that combining acyclovir with cisplatin and radiation significantly decreases the viability of the EBV-infected C666-1 cell line. Western blot quantification revealed a resultant increase of thymidine kinase (TK) and apoptosis-inducing mediators, cleaved PARP (cPARP) and phosphorylated ERK (pERK). These studies suggest that the addition of anti-viral drugs to frontline chemoradiation may improve outcomes in patients treated for EBV-related NPC and future in vivo and clinical studies are needed.

中文翻译：

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阿昔洛韦改善含有爱泼斯坦巴尔病毒基因组的鼻咽癌化学放射治疗的功效

鼻咽癌（NPC）是东亚地区的一种恶性肿瘤，由爱泼斯坦-巴尔病毒（EBV）介导的上皮细胞癌变引起。鼻咽癌的护理标准包括放疗和化疗。尽管治疗效果继续改善，但预计五年后将有多达50％的患者复发，因此需要其他创新治疗方案。我们认为，实现这一目标的潜在方法是针对恶性转化的潜在原因，即EBV。EBV逃避免疫监视的一种方法是进行潜伏期复制，在此期间，免疫原性蛋白的EBV表达降低。然而，已知化学辐射可驱动EBV从潜伏期转变为裂解阶段。这为利用抗病毒药物靶向EBV感染的细胞创造了机会。实际上，我们发现将阿昔洛韦与顺铂和放射线结合使用会显着降低EBV感染的C666-1细胞系的生存能力。Western blot定量显示胸苷激酶（TK）和凋亡诱导介体，PARP裂解（cPARP）和磷酸化ERK（pERK）的合成增加。这些研究表明，在一线化学放疗中添加抗病毒药物可能会改善接受EBV相关性NPC治疗的患者的预后，还需要进一步的体内和临床研究。Western blot定量显示胸苷激酶（TK）和凋亡诱导介体，PARP裂解（cPARP）和磷酸化ERK（pERK）的合成增加。这些研究表明，在一线化学放疗中添加抗病毒药物可能会改善接受EBV相关性NPC治疗的患者的预后，还需要进一步的体内和临床研究。Western blot定量显示胸苷激酶（TK）和凋亡诱导介体，PARP裂解（cPARP）和磷酸化ERK（pERK）的合成增加。这些研究表明，在一线化学放疗中添加抗病毒药物可能会改善接受EBV相关性NPC治疗的患者的预后，还需要进一步的体内和临床研究。