Varricchio Alanah, Yool Andrea J
School of Biomedicine, Institute for Photonics and Advanced Sensing, University of Adelaide, Adelaide, SA 5005, Australia.
Cancers (Basel). 2023 Jan 30;15(3):849. doi: 10.3390/cancers15030849.
Current therapies for Glioblastoma multiforme (GBM) focus on eradicating primary tumors using radiotherapy, chemotherapy and surgical resection, but have limited success in controlling the invasive spread of glioma cells into a healthy brain, the major factor driving short survival times for patients post-diagnosis. Transcriptomic analyses of GBM biopsies reveal clusters of membrane signaling proteins that in combination serve as robust prognostic indicators, including aquaporins and ion channels, which are upregulated in GBM and implicated in enhanced glioblastoma motility. Accumulating evidence supports our proposal that the concurrent pharmacological targeting of selected subclasses of aquaporins and ion channels could impede glioblastoma invasiveness by impairing key cellular motility pathways. Optimal sets of channels to be selected as targets for combined therapies could be tailored to the GBM cancer subtype, taking advantage of differences in patterns of expression between channels that are characteristic of GBM subtypes, as well as distinguishing them from non-cancerous brain cells such as neurons and glia. Focusing agents on a unique channel fingerprint in GBM would further allow combined agents to be administered at near threshold doses, potentially reducing off-target toxicity. Adjunct therapies which confine GBM tumors to their primary sites during clinical treatments would offer profound advantages for treatment efficacy.
多形性胶质母细胞瘤（GBM）的现有治疗方法主要集中在通过放疗、化疗和手术切除来根除原发性肿瘤，但在控制胶质瘤细胞向健康脑组织的侵袭性扩散方面成效有限，而这种侵袭性扩散是导致患者确诊后生存期较短的主要因素。对GBM活检组织的转录组分析揭示了膜信号蛋白簇，这些蛋白共同构成了强大的预后指标，包括水通道蛋白和离子通道，它们在GBM中上调并与增强的胶质母细胞瘤运动性有关。越来越多的证据支持我们的提议，即同时对选定亚类的水通道蛋白和离子通道进行药理学靶向，可能通过损害关键的细胞运动途径来阻碍胶质母细胞瘤的侵袭性。作为联合治疗靶点选择的最佳通道组合可以根据GBM癌症亚型进行定制，利用GBM亚型特有的通道表达模式差异，以及将它们与神经元和神经胶质等非癌性脑细胞区分开来。将药物作用于GBM中独特的通道指纹，还将使联合药物能够以接近阈值的剂量给药， potentially reducing off-target toxicity. Adjunct therapies which confine GBM tumors to their primary sites during clinical treatments would offer profound advantages for treatment efficacy.（原文此处有误，正确翻译应为：这可能会降低脱靶毒性。在临床治疗期间将GBM肿瘤限制在其原发部位的辅助治疗将对治疗效果带来显著优势。）
