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WINDOW consortium: A path towards increased therapy efficacy against glioblastoma
Drug Resistance Updates ( IF 24.3 ) Pub Date : 2018-10-30 , DOI: 10.1016/j.drup.2018.10.001
Kulsoom U. Abdul , Megan Houweling , Fredrik Svensson , Ravi S. Narayan , Fleur M.G. Cornelissen , Asli Küçükosmanoglu , Emmanouil Metzakopian , Colin Watts , David Bailey , Tom Wurdinger , Bart A. Westerman

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.



中文翻译:

WINDOW财团:增强治疗胶质母细胞瘤疗效的途径

胶质母细胞瘤是最常见和恶性的脑癌形式,其标准治疗方法是最大程度的手术切除,放疗和化疗。尽管采取了这些干预措施,但平均总生存期仍不到15个月,在此期间,整个大脑都发生了广泛的肿瘤浸润。大脑中产生的转移细胞的特征是化疗耐药性和广泛的肿瘤内异质性。攻击细胞内抗性机制以及细胞间异质性的正交方法对于阻止肿瘤进展是必要的。因此,我们建立了WINDOW联盟(通过克服疾病恶化而改善新诊断患者的窗口),我们正在制定一项策略,以合理选择和开发有效的抗胶质母细胞瘤疗法。在这里,我们概述了治疗胶质母细胞瘤所面临的许多挑战,包括选择可预防治疗耐药性的药物组合,对改善血脑屏障渗透性的药物的需求以及应对患者体内异种细胞群体的策略的需求。总之,这构成了我们攻击胶质母细胞瘤策略的骨干。

更新日期:2018-10-30
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