Glioblastoma is an aggressive, incurable brain cancer with poor five-year survival rates of around 13% despite multimodal treatment with surgery, DNA-damaging chemoradiotherapy and the recent addition of Tumour Treating Fields (TTFields). As such, there is an urgent need to improve our current understanding of cellular responses to TTFields using more clinically and surgically relevant models, which reflect the profound spatial heterogeneity within glioblastoma, and leverage these biological insights to inform the rational design of more effective therapeutic strategies incorporating TTFields. We have recently reported the use of preclinical TTFields using the inovitroTMsystem within 2D glioma stem-like cell (GSC) models and demonstrated significant cytotoxicity enhancement when co-applied with a range of therapeutically approved and preclinical DNA damage response inhibitors (DDRi) and chemoradiotherapy. Here we report the development and optimisation of preclinical TTFields delivery within more clinically relevant 3D scaffold-based primary GSC models of spatial heterogeneity, and highlight some initial enhancement of TTFields potency with temozolomide and clinically approved PARP inhibitors (PARPi). These studies, therefore, represent an important platform for further preclinical assessment of TTFields-based therapeutic strategies within clinically relevant 3D GSC models, aimed towards accelerating clinical trial implementation and the ultimate goal of improving the persistently dire survival rates for these patients.
胶质母细胞瘤是一种侵袭性强、无法治愈的脑癌，尽管采用手术、DNA损伤性放化疗及近期加入的肿瘤治疗电场等多模式治疗，其五年生存率仍低至约13%。因此，亟需通过更具临床和手术相关性的模型来深化当前对细胞响应肿瘤治疗电场的理解，这些模型应能反映胶质母细胞瘤内部显著的空间异质性，并利用这些生物学洞见指导整合肿瘤治疗电场的更有效治疗策略的理性设计。我们近期报道了在二维胶质瘤干细胞样细胞模型中应用inovitroTM系统进行临床前肿瘤治疗电场研究，证明其与多种已获批临床及临床前的DNA损伤反应抑制剂和放化疗联用时能显著增强细胞毒性。本文重点介绍了在更具临床相关性的三维支架原代胶质瘤干细胞样细胞空间异质性模型中，临床前肿瘤治疗电场递送系统的开发与优化，并初步展示了其与替莫唑胺及临床获批PARP抑制剂联用时的增效作用。这些研究为在临床相关三维胶质瘤干细胞样细胞模型中进一步开展基于肿瘤治疗电场的治疗策略临床前评估提供了重要平台，旨在加速临床试验实施，最终改善这类患者持续严峻的生存率。
肿瘤(癌症)患者之家