Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Biochim Biophys Acta Rev Cancer. 2018 Apr;1869(2):175-188. doi: 10.1016/j.bbcan.2018.01.004. Epub 2018 Jan 31.
De-regulated cellular energetics is an emerging hallmark of cancer with alterations to glycolysis, oxidative phosphorylation, the pentose phosphate pathway, lipid oxidation and synthesis and amino acid metabolism. Understanding and targeting of metabolic reprogramming in cancers may yield new treatment options, but metabolic heterogeneity and plasticity complicate this strategy. One highly heterogeneous cancer for which current treatments ultimately fail is the deadly brain tumor glioblastoma. Therapeutic resistance, within glioblastoma and other solid tumors, is thought to be linked to subsets of tumor initiating cells, also known as cancer stem cells. Recent profiling of glioblastoma and brain tumor initiating cells reveals changes in metabolism, as compiled here, that may be more broadly applicable. We will summarize the profound role for metabolism in tumor progression and therapeutic resistance and discuss current approaches to target glioma metabolism to improve standard of care.
细胞能量代谢失调是癌症的一个新标志，表现为糖酵解、氧化磷酸化、磷酸戊糖途径、脂质氧化和合成以及氨基酸代谢的改变。了解和靶向癌症中的代谢重编程可能会产生新的治疗选择，但代谢异质性和可塑性使这一策略变得复杂。目前治疗最终失败的一种高度异质性癌症是致命的脑肿瘤胶质母细胞瘤。胶质母细胞瘤和其他实体瘤中的治疗耐药性被认为与肿瘤起始细胞亚群（也称为癌症干细胞）有关。最近对胶质母细胞瘤和脑肿瘤起始细胞的分析揭示了代谢变化，如本文所述，这些变化可能具有更广泛的适用性。我们将总结代谢在肿瘤进展和治疗耐药性中的深远作用，并讨论当前靶向神经胶质瘤代谢以改善标准治疗的方法。
