Abstract:
Despite numerous advancements in the last decade, human gliomas such as astrocytoma and glioblastoma multiforme have the worst prognoses among all cancers. Anti-psychotic drugs are commonly prescribed to treat mental disorders among cancer patients, and growing empirical evidence has revealed their antitumor, anti-metastatic, anti-angiogenic, anti-proliferative, chemo-preventive, and neo-adjuvant efficacies in various in vitro, in vivo, and clinical glioma models. Anti-psychotic drugs have drawn the attention of physicians and researchers owing to their beneficial effects in the prevention and treatment of gliomas. This review highlights data on the therapeutic potential of various anti-psychotic drugs as anti-proliferative, chemopreventive, and anti-angiogenic agents in various glioma models via the modulation of upstream and downstream molecular targets involved in apoptosis, autophagy, oxidative stress, inflammation, and the cell cycle in in vitro and in vivo preclinical and clinical stages among glioma patients. The ability of anti-psychotic drugs to modulate various signaling pathways and multidrug resistance-conferring proteins that enhance the efficacy of chemotherapeutic drugs with low side-effects exemplifies their great potential as neo-adjuvants and potential chemotherapeutics in single or multimodal treatment approach. Moreover, anti-psychotic drugs confer the ability to induce glioma into oligodendrocyte-like cells and neuronal-like phenotype cells with reversal of epigenetic alterations through inhibition of histone deacetylase further rationalize their use in glioma treatment. The improved understanding of anti-psychotic drugs as potential chemotherapeutic drugs or as neo-adjuvants will provide better information for their use globally as affordable, well-tolerated, and effective anticancer agents for human glioma.
摘要:
尽管在过去的十年中取得了许多进步,人脑胶质瘤如星形细胞瘤和多形性胶质母细胞瘤在所有癌症中预后最差。抗精神病药物通常用于治疗癌症患者的精神障碍,越来越多的经验证据揭示了它们的抗肿瘤作用,抗转移性,抗血管生成,抗增殖,化学预防,和新佐剂在各种体外的功效,在体内,和临床神经胶质瘤模型。抗精神病药物由于其在神经胶质瘤的预防和治疗中的有益作用而引起了医生和研究人员的注意。这篇综述强调了各种抗精神病药物作为抗增殖药物的治疗潜力的数据,化学预防,和抗血管生成剂在各种胶质瘤模型中通过调节参与凋亡的上游和下游分子靶标,自噬,氧化应激,炎症,以及胶质瘤患者体内外临床前和临床阶段的细胞周期。抗精神病药物调节各种信号传导途径和赋予多药抗性的蛋白质的能力增强具有低副作用的化疗药物的功效,这表明了它们在单或多模式治疗方法中作为新佐剂和潜在化疗药物的巨大潜力。此外,抗精神病药物通过抑制组蛋白去乙酰化酶,赋予神经胶质瘤诱导成少突胶质细胞样细胞和神经元样表型细胞的能力,逆转表观遗传学改变,进一步使其在神经胶质瘤治疗中的应用合理化.对抗精神病药物作为潜在化疗药物或新佐剂的进一步了解将为其在全球范围内的使用提供更好的信息,耐受性良好,和人类神经胶质瘤的有效抗癌剂。