Biology Department, Boston College, 140 Commonwealth Ave, Chestnut Hill, MA, 02467, USA.
Human Metabolome Technologies America, 24 Denby Rd., Boston, MA, 02134, USA.
Neurochem Res. 2019 Oct;44(10):2392-2404. doi: 10.1007/s11064-019-02795-4. Epub 2019 Apr 25.
No major advances have been made in improving overall survival for glioblastoma (GBM) in almost 100 years. The current standard of care (SOC) for GBM involves immediate surgical resection followed by radiotherapy with concomitant temozolomide chemotherapy. Corticosteroid (dexamethasone) is often prescribed to GBM patients to reduce tumor edema and inflammation. The SOC disrupts the glutamate-glutamine cycle thus increasing availability of glucose and glutamine in the tumor microenvironment. Glucose and glutamine are the prime fermentable fuels that underlie therapy resistance and drive GBM growth through substrate level phosphorylation in the cytoplasm and the mitochondria, respectively. Emerging evidence indicates that ketogenic metabolic therapy (KMT) can reduce glucose availability while elevating ketone bodies that are neuroprotective and non-fermentable. Information is presented from preclinical and case report studies showing how KMT could target tumor cells without causing neurochemical damage thus improving progression free and overall survival for patients with GBM.
近 100 年来，胶质母细胞瘤（GBM）的整体生存率没有明显提高。目前 GBM 的标准治疗（SOC）包括立即手术切除，然后进行放疗联合替莫唑胺化疗。皮质类固醇（地塞米松）通常开给 GBM 患者，以减轻肿瘤水肿和炎症。SOC 破坏了谷氨酸-谷氨酰胺循环，从而增加了肿瘤微环境中葡萄糖和谷氨酰胺的可用性。葡萄糖和谷氨酰胺是主要的可发酵燃料，它们通过细胞质和线粒体中的底物水平磷酸化，分别导致治疗耐药和驱动 GBM 生长。新出现的证据表明，生酮代谢疗法（KMT）可以降低葡萄糖的可用性，同时提高神经保护和不可发酵的酮体。从临床前和病例报告研究中提供了信息，表明 KMT 如何在不造成神经化学损伤的情况下靶向肿瘤细胞，从而改善 GBM 患者的无进展生存期和总生存期。
