Glioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O⁶ methylguanine DNA methyltransferase (MGMT ) that renders the tumors resistant to temozolomide (TMZ). We hypothesized that pretreatment with bortezomib (BTZ) 48 hours prior to TMZ to deplete MGMT levels would be safe and tolerated by patients with recurrent GBM harboring unmethylated MGMT promoter. The secondary objective was to investigate whether 26S proteasome blockade may enhance differentiation of cytotoxic immune subsets to impact treatment responses measured by radiological criteria and clinical outcomes.

中文翻译：

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连续硼替佐米和替莫唑胺治疗可促进具有阳性临床结果的胶质母细胞瘤患者的免疫反应：一项 1B 期研究。

胶质母细胞瘤 (GBM) 是一种侵袭性恶性脑肿瘤，在最佳可用多模式治疗后的中位生存期约为 15 个月。复发是不可避免的，主要是由于 O ⁶甲基鸟嘌呤 DNA 甲基转移酶 ( MGMT ) 使肿瘤对替莫唑胺 (TMZ) 产生耐药性。我们假设在 TMZ 前 48 小时用硼替佐米 (BTZ) 进行预处理以消耗 MGMT 水平是安全的，并且可以被具有未甲基化MGMT启动子的复发性 GBM 患者耐受。次要目的是研究 26S 蛋白酶体阻断是否可以增强细胞毒性免疫亚群的分化，以影响通过放射学标准和临床结果测量的治疗反应。