Woolf Eric C, Scheck Adrienne C
Neuro-Oncology Research, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013.
J Lipid Res. 2015 Jan;56(1):5-10. doi: 10.1194/jlr.R046797. Epub 2014 Feb 6.
Advances in our understanding of glioma biology has led to an increase in targeted therapies in preclinical and clinical trials; however, cellular heterogeneity often precludes the targeted molecules from being found on all glioma cells, thus reducing the efficacy of these treatments. In contrast, one trait shared by virtually all tumor cells is altered (dysregulated) metabolism. Tumor cells have an increased reliance on glucose, suggesting that treatments affecting cellular metabolism may be an effective method to improve current therapies. Indeed, metabolism has been a focus of cancer research in the last few years, as many pathways long associated with tumor growth have been found to intersect metabolic pathways in the cell. The ketogenic diet (high fat, low carbohydrate and protein), caloric restriction, and fasting all cause a metabolic change, specifically, a reduction in blood glucose and an increase in blood ketones. We, and others, have demonstrated that these metabolic changes improve survival in animal models of malignant gliomas and can potentiate the anti-tumor effect of chemotherapies and radiation treatment. In this review we discuss the use of metabolic alteration for the treatment of malignant brain tumors.
我们对胶质瘤生物学认识的进展促使临床前和临床试验中的靶向治疗有所增加；然而，细胞异质性常常使靶向分子无法在所有胶质瘤细胞上被发现，从而降低了这些治疗的效果。相比之下，几乎所有肿瘤细胞共有的一个特征是代谢改变（失调）。肿瘤细胞对葡萄糖的依赖性增加，这表明影响细胞代谢的治疗方法可能是改善当前疗法的有效手段。事实上，在过去几年中，代谢一直是癌症研究的重点，因为许多长期以来与肿瘤生长相关的途径已被发现与细胞内的代谢途径相互交叉。生酮饮食（高脂肪、低碳水化合物和蛋白质）、热量限制和禁食都会引起代谢变化，具体而言，就是血糖降低和血酮增加。我们以及其他研究人员已证明，这些代谢变化可提高恶性胶质瘤动物模型的生存率，并能增强化疗和放射治疗的抗肿瘤效果。在这篇综述中，我们讨论利用代谢改变来治疗恶性脑肿瘤。
