Development and clinical assessment of novel biomarker drugs targeting SSAT1 for detection and therapeutic monitoring of glioblastoma

多形性胶质母细胞瘤(GBM)是成人最常见的脑肿瘤，对患者来说是死刑。GBM患者(确诊后平均存活14-16个月)的存活率非常低，部分原因是早期检测方法有限，缺乏有效的治疗选择。建议的研究将建立重要的 加拿大卫生部批准使用金刚烷胺和金刚乙胺等药物作为监测GBM的安全、有效和负担得起的方法的证据。该方法是基于GBM细胞中一种名为精胺/精胺N-乙酰转移酶(SSAT1)的关键酶的过度生产。在GBM中SSAT1表达增加导致细胞代谢增加 在GBM患者的血液或尿液中检测到的药物。研究将为药物金刚烷胺在检测细胞培养和公认的啮齿动物脑瘤模型中检测GBM的有效性提供证据。其他化学结构与金刚烷胺相似的药物将在细胞培养和动物模型中进行检查，以优化药物 脑穿透和肿瘤细胞活性的生物标记物。研究结束时，将对GBM患者选择的药物生物标记物进行初步评估，以确定临床应用脑瘤的可行性。我们的工业合作伙伴BioMark Diagnostics将利用这些从床到床的研究来帮助改进对患者的识别和护理 使用GB

Glioblastoma multiforme (GBM) is the most common brain tumor in adults and is a death sentence for patients. The strikingly poor survival for patients with GBM (average survival 14- 16 months following diagnosis) is due in part to limited early detection methods and an absence of effective therapeutic options. The studies proposed would establish important evidence for the use of Health Canada approved drugs such as amantadine and rimantadine as a safe, effective and affordable way to monitor GBM. The method is based on the overproduction of a key enzyme in GBM cells called spermine/ spermadine n-acetyl transferase (SSAT1). The increased SSAT1 expression in GBM results in increased metabolism of the drug which is detected in the blood or urine of patients with GBM. Studies will provide evidence for the effectiveness of the drug amantadine, in detecting GBM in both cell culture and accepted rodent brain tumor models. Other drugs with similar chemical structure to amantadine will be examined in the cell culture and animal models to optimize the drug biomarker for brain penetration and tumor cell activity. The studies will conclude with an initial assessment of the selected drug biomarker in patients with GBM to determine feasibility for clinical brain tumor applications. These bench to bedside studies will be utilized by our industrial partner, BioMark Diagnostics, to help improve identification and care for patients with GB