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）是成人中最常见的脑肿瘤，对患者来说是死刑判决。GBM患者的生存率非常低（诊断后平均存活14- 16个月），部分原因是早期发现方法有限，缺乏有效的治疗选择。拟议的研究将为使用加拿大卫生部批准的药物（如金刚烷胺和金刚乙胺）作为一种安全、有效和负担得起的监测GBM的方法提供重要证据。该方法基于GBM细胞中一种关键酶的过量产生，这种酶称为精胺/精胺n-乙酰转移酶（SSAT1）。在GBM中，SSAT1表达增加导致药物代谢增加，可在GBM患者的血液或尿液中检测到。研究将为药物金刚烷胺在细胞培养和公认的啮齿动物脑肿瘤模型中检测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研究，以优化药物生物标志物的脑渗透和肿瘤细胞活性。研究结束时，将对所选药物生物标志物在GBM患者中的应用进行初步评估，以确定其在脑肿瘤临床应用的可行性。我们的工业合作伙伴BioMark Diagnostics将利用这些从实验室到床边的研究来帮助改善对GB患者的识别和护理

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 importantevidence 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 thedrug 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 drugbiomarker 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 patientswith GB