Bortezomib-induced Epstein-Barr virus and Kaposi sarcoma herpesvirus lytic gene expression: oncolytic strategies.
Bortezomib-induced Epstein-Barr virus and Kaposi sarcoma herpesvirus lytic gene expression: oncolytic strategies.
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DOI：
10.1097/cco.0b013e3283499c37
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发表时间：
2011-09
影响因子：
3.4
通讯作者：
Reid EG
中科院分区：
文献类型：
--
作者：
Reid EG
γ疱疹病毒是导致大量病毒相关人类癌症的原因，特别是在免疫功能低下的个体中。利用病毒裂解激活潜伏感染肿瘤的方法代表了一种新的抗肿瘤治疗策略。蛋白酶体抑制剂硼替佐米已被证明是伽马疱疹病毒裂解周期的有效激活剂，并在伽马疱疹病毒相关恶性肿瘤的病例报告中显示出活性。虽然最初的报道涉及NF-kappaB途径的抑制，但最近的研究发现了硼替佐米介导的γ疱疹病毒裂解诱导和对携带它们的恶性肿瘤的活性的替代途径。进一步探索蛋白酶体抑制作为溶瘤策略是有必要的，并且需要临床/转化试验来确定γ疱疹病毒的裂解诱导是否与硼替佐米的临床反应相关，如果相关，则优化这种溶瘤策略。
Gamma herpesviruses are responsible for a substantial proportion of virus-associated human cancers, particularly in immunocompromised individuals. Methods that employ lytic activation of viruses latently infecting tumors represent a novel strategy of anti-neoplastic therapy. The proteasome inhibitor bortezomib has been shown to be a potent activator of gamma herpesvirus lytic cycle and has demonstrated activity in case reports of gamma herpesvirus-related malignancies. While initial reports implicated inhibition of the NF-kappaB pathway, more recent studies identify alternative pathways responsible for bortezomib-mediated lytic induction of gammaherpes viruses and activity against the malignancies that harbor them. Further exploration of proteasome inhibition as an oncolytic strategy is warranted and will require clinical/translational trials to identify whether lytic induction of gamma herpesviruses correlates with clinical response to bortezomib, and, if so, to optimize this oncolytic strategy.