Griffin Michaela, Khan Raheela, Basu Surajit, Smith Stuart
Children's Brain Tumour Research Centre, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK.
Division of Medical Sciences and Graduate Entry Medicine, Royal Derby Hospital, University of Nottingham, Nottingham NG7 2RD, UK.
Cancers (Basel). 2020 Oct 21;12(10):3068. doi: 10.3390/cancers12103068.
Glioblastoma multiforme (GBM) is a lethal brain cancer with an average survival of 14-15 months even with exhaustive treatment. High grade gliomas (HGG) represent the leading cause of CNS cancer-related death in children and adults due to the aggressive nature of the tumour and limited treatment options. The scarcity of treatment available for GBM has opened the field to new modalities such as electrotherapy. Previous studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence indicates that not only are ion channels key in regulating electrical signaling and membrane potential of excitable cells, they perform a crucial role in the development and neoplastic progression of brain tumours. Unlike other tissue types, neural tissue is intrinsically electrically active and reliant on ion channels and their function. Ion channels are essential in cell cycle control, invasion and migration of cancer cells and therefore present as valuable therapeutic targets. This review aims to discuss the role that ion channels hold in gliomagenesis and whether we can target and exploit these channels to provide new therapeutic targets and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.
多形性胶质母细胞瘤(GBM)是一种致命的脑癌,即使经过彻底治疗,平均生存期也只有14至15个月。由于肿瘤的侵袭性和有限的治疗选择,高级别胶质瘤(HGG)是儿童和成人中枢神经系统癌症相关死亡的主要原因。GBM可用治疗方法的匮乏为电疗法等新的治疗方式开辟了领域。先前的研究已经确定了电疗法与化疗联合使用的临床益处,但其作用机制尚不清楚。越来越多的证据表明,离子通道不仅在调节可兴奋细胞的电信号和膜电位方面起关键作用,它们在脑肿瘤的发生和肿瘤进展中也起着至关重要的作用。与其他组织类型不同,神经组织具有内在的电活性,依赖于离子通道及其功能。离子通道在癌细胞的细胞周期控制、侵袭和迁移中至关重要,因此是有价值的治疗靶点。本综述旨在讨论离子通道在胶质瘤发生中的作用,以及我们是否可以靶向和利用这些通道来提供新的治疗靶点,以及离子通道是否是电疗法新发现成功的机制关键。