Umans Robyn A, Sontheimer Harald
Center for Glial Biology in Health and Disease, Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, VA, 24016, USA.
Center for Glial Biology in Health and Disease, Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, VA, 24016, USA.
Neurosci Res. 2018 Jan;126:22-30. doi: 10.1016/j.neures.2017.09.010. Epub 2017 Oct 18.
Malignant gliomas are glial-derived, primary brain tumors that carry poor prognosis. Existing therapeutics are largely ineffective and dramatically affect quality of life. The standard of care details a taxing combination of surgical resection, radiation of the resection cavity, and temozolomide (TMZ) chemotherapy, with treatment extending life by only an average of months (Maher et al., 2001; Stupp et al., 2005). Despite scientific and technological advancement, surgery remains the most important treatment modality. Therapeutic obstacles include xenobiotic protection conveyed by the blood-brain barrier (Zhang et al., 2015), invasiveness and therapeutic resistance of tumor cell populations (Bao et al., 2006), and distinctive attributes of secondary glioma occurrence (Ohgaki and Kleihues, 2013). While these brain malignancies can be classified by grade or grouped by molecular subclass, each tumor presents itself as its own complication. Based on all of these obstacles, new therapeutic approaches are urgently needed. These will likely emerge from numerous exciting studies of glioma biology that are ongoing and reviewed here. These show unexpected roles for ion channels, amino-acid transporters, and connexin gap junctions in supporting the invasive growth of gliomas. These studies have identified a number of proteins that may be targeted for therapy in the future.
恶性胶质瘤是源自神经胶质细胞的原发性脑肿瘤,预后较差。现有的治疗方法大多无效,且会严重影响生活质量。护理标准详细说明了手术切除、切除腔放疗和替莫唑胺(TMZ)化疗这一繁重的联合治疗方案,该治疗方案仅能将患者的生命平均延长数月(马赫等人,2001年;施图普等人,2005年)。尽管科技不断进步,但手术仍然是最重要的治疗方式。治疗障碍包括血脑屏障所提供的异生物质保护(张等人,2015年)、肿瘤细胞群体的侵袭性和治疗抗性(鲍等人,2006年)以及继发性胶质瘤发生的独特特征(大垣和克莱休斯,2013年)。虽然这些脑恶性肿瘤可以按分级分类或按分子亚类分组,但每个肿瘤都有其自身的复杂性。基于所有这些障碍,迫切需要新的治疗方法。这些方法可能会源自目前正在进行并在此处进行综述的众多关于胶质瘤生物学的令人兴奋的研究。这些研究显示了离子通道、氨基酸转运体和连接蛋白间隙连接在支持胶质瘤侵袭性生长方面的意外作用。这些研究已经确定了一些未来可能成为治疗靶点的蛋白质。