Department of Neurosurgery, Brain Tumor Center Amsterdam, Amsterdam University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HZ, Amsterdam, Netherlands.
IOTA Pharmaceuticals Ltd, St Johns Innovation Centre, Cowley Road, Cambridge, CB4 0WS, United Kingdom.
Drug Resist Updat. 2018 Sep;40:17-24. doi: 10.1016/j.drup.2018.10.001. Epub 2018 Oct 30.
Glioblastoma is the most common and malignant form of brain cancer, for which the standard treatment is maximal surgical resection, radiotherapy and chemotherapy. Despite these interventions, mean overall survival remains less than 15 months, during which extensive tumor infiltration throughout the brain occurs. The resulting metastasized cells in the brain are characterized by chemotherapy resistance and extensive intratumoral heterogeneity. An orthogonal approach attacking both intracellular resistance mechanisms as well as intercellular heterogeneity is necessary to halt tumor progression. For this reason, we established the WINDOW Consortium (Window for Improvement for Newly Diagnosed patients by Overcoming disease Worsening), in which we are establishing a strategy for rational selection and development of effective therapies against glioblastoma. Here, we overview the many challenges posed in treating glioblastoma, including selection of drug combinations that prevent therapy resistance, the need for drugs that have improved blood brain barrier penetration and strategies to counter heterogeneous cell populations within patients. Together, this forms the backbone of our strategy to attack glioblastoma.
胶质母细胞瘤是最常见和最恶性的脑癌，其标准治疗方法是最大限度的手术切除、放疗和化疗。尽管进行了这些干预，平均总生存期仍不到 15 个月，在此期间，肿瘤会广泛渗透到大脑中。大脑中转移的细胞具有化疗耐药性和广泛的肿瘤内异质性。为了阻止肿瘤的进展，有必要采用一种正交的方法来攻击细胞内的耐药机制和细胞间的异质性。出于这个原因，我们成立了 WINDOW 联盟（通过克服疾病恶化来改善新诊断患者的机会窗口），我们正在制定一种针对胶质母细胞瘤的合理选择和开发有效治疗方法的策略。在这里，我们概述了治疗胶质母细胞瘤所面临的许多挑战，包括选择防止治疗耐药性的药物组合、需要具有改善血脑屏障穿透性的药物以及针对患者体内异质细胞群体的策略。这些共同构成了我们攻击胶质母细胞瘤的策略的核心。
