Targeting Energy Metabolism to Overcome Therapeutic Resistance of Glioblastoma and Tumor-associated Edema
Targeting Energy Metabolism to Overcome Therapeutic Resistance of Glioblastoma and Tumor-associated Edema
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DOI：
10.36255/exonpublications.gliomas.2021.chapter7
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
B. Dasgupta;Yoshihisa Hirota;Y. Fujii;Natsuki Osaka;Doshun Ito;D. Plas;A. Sasaki
中科院分区：
文献类型：
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作者：
B. Dasgupta;Yoshihisa Hirota;Y. Fujii;Natsuki Osaka;Doshun Ito;D. Plas;A. Sasaki
胶质母细胞瘤是人类最致命的恶性肿瘤之一。与单独放疗相比，目前的护理标准平均延长了2个月的预期寿命，患者的中位生存期为14.6个月。胶质母细胞瘤是一种不同程度的异质肿瘤，具有固有的耐放化疗特性。这些限制了原发和复发肿瘤的治疗选择。重要的是，胶质母细胞瘤的进展通常伴有脑水肿，这是影响该疾病临床病程和预后的重要发病原因。免疫抑制皮质类固醇一直是胶质母细胞瘤相关水肿的主要治疗方法。然而，这种效果是暂时的，并且由于皮质类固醇在目标区域之外的作用而伴有不良反应。过去二十年的研究已经揭示了代谢重编程在胶质瘤发生和治疗耐药期间赋予生存优势的重要作用。本章介绍了最近发现的两种能量代谢途径：amp激活的激酶介导的应激弹性胶质母细胞瘤生长，以及鸟苷-5 ' -三磷酸(GTP)-代谢重编程，使合成代谢生长和辐射抗性。我们讨论了目前可用的药物的潜在临床效用，这些药物可以靶向这些代谢途径来抑制胶质母细胞瘤的恶性生长，并提高当前胶质母细胞瘤治疗的疗效。
ABSTRACT Glioblastoma remains among the most lethal of human malignancies. The current standard of care prolongs life expectancy about 2 months on average compared to from radiation therapy alone, leading to a median patient survival of 14.6 months. Glioblastoma is heterogenous tumor at various levels, and intrinsically resistance to radiation and chemotherapy. These limits therapeutic options for both primary and recurrent tumors. Importantly, glioblastoma progression is often accompanied by cerebral edema, a significant cause of morbidity that influences the clinical course and prognosis of the disease. Immunosuppressive corticosteroids have been the primary treatment for glioblastoma-associated edema. However, the effect is temporary and accompanied by adverse effects due to the action of corticosteroids outside of the targeted area. Research over the past two decades has unveiled a significant role for metabolic reprogramming that confers a survival advantage during gliomagenesis and therapeutic resistance. This chapter introduces the recent discoveries of two energy metabolism pathways: AMP-activated kinase-mediated stress-resilient glioblastoma growth, and Guanosine-5’-triphosphate (GTP)- metabolic reprogramming that renders anabolic growth and radioresistance. We discuss the potential clinical utility of currently available medicine that could target these metabolic pathways to suppress malignant growth of glioblastoma and increase the efficacy of the current glioblastoma therapy.