Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors.
Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors.
复制标题
作者：
我们研究了使用药物调节病毒基因表达的可能性，以便将放射治疗靶向肿瘤组织。在鼠异种移植模型中，我们先前已经显示了[125 I] 2 '-氟-2'-脱氧-β-D-5-碘尿嘧啶阿拉伯呋喃糖苷（[125 I]FIAU）对表达EB病毒（EBV）-胸苷激酶（TK）的肿瘤的靶向作用。在这里，我们将这些结果扩展到治疗性放射性药物[131 I]FIAU的靶向，以减缓或停止肿瘤生长或实现肿瘤消退。这些结果在具有组成型表达EBV-TK的肿瘤的异种移植物中以及在具有天然感染的EBV肿瘤细胞系的异种移植物中实现。伯基特淋巴瘤和胃癌需要通过硼替佐米预处理激活病毒基因表达。在硼替佐米激活后，在自然感染的卡波西肉瘤疱疹病毒（KSHV）肿瘤中也可以实现肿瘤生长的显著变化。硼替佐米诱导的酶靶向放射（BETR）治疗阐明了通过酶调节肿瘤基因表达来实现靶向放射治疗的可能性。
We investigated the possibility of using a pharmacologic agent to modulate viral gene expression in order to target radiotherapy to tumor tissue. In a murine xenograft model, we had previously shown targeting of [125I]2'-fluoro-2'-deoxy-beta-D-5-iodouracilarabinofuranoside ([125I]FIAU) to tumors engineered to express the Epstein-Barr virus (EBV)-thymidine kinase (TK). Here we extend those results to targeting of a therapeutic radiopharmaceutical [131I]FIAU to slow or stop tumor growth or to achieve tumor regression. These outcomes were achieved in xenografts with tumors that constitutively expressed the EBV-TK, as well as with naturally-infected EBV tumor cell lines. Burkitt's lymphoma and gastric carcinoma required activation of viral gene expression by pretreatment with bortezomib. Marked changes in tumor growth could also be achieved in naturally-infected Kaposi's sarcoma herpesvirus (KSHV) tumors following bortezomib activation. Bortezomib-induced enzyme-targeted radiation (BETR) therapy illustrates the possibility of pharmacologically modulating tumor gene expression to effect targeted radiotherapy.