Thomas Tom M, Yu John S
Maxine-Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Maxine-Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Cancer Lett. 2017 Nov 1;408:174-181. doi: 10.1016/j.canlet.2017.07.014. Epub 2017 Jul 22.
Cancer metabolism has emerged as one of the most interesting old ideas being revisited from a new perspective. In the early 20th century Otto Warburg declared metabolism the prime cause in a disease of many secondary causes, and this statement seems more prescient in view of modern expositions into the true nature of tumor evolution. As the complexity of tumor heterogeneity becomes more clear from a genetic perspective, it is important to consider the inevitably heterogeneous metabolic components of the tumor and the tumor microenvironment. High grade gliomas remain one of the most difficult to treat solid tumors, due in part to the highly vascularized nature of the tumor and the maintenance of more resistant stem-like subpopulations within the tumor. Maintenance of glioma stem cells (GSCs) requires specific alterations within the cells and the greater tumor microenvironment with regards to signaling and metabolism. Specific niches within gliomas help foster the survival of stem-like sub-populations of cells with high tumorigenicity and high metabolic plasticity. Understanding these maintenance pathways and the metabolic dependencies within the niche may highlight potential avenues of addressing tumor resistance and recurrence in glioma patients.
癌症代谢已成为从新视角重新审视的最有趣的旧观点之一。在20世纪初,奥托·瓦尔堡宣称代谢是一种具有多种次要病因的疾病的主要病因,鉴于现代对肿瘤演变真实本质的阐述,这一说法似乎更具先见之明。从遗传学角度来看,肿瘤异质性的复杂性愈发清晰,因此考虑肿瘤及其微环境中不可避免的异质代谢成分至关重要。高级别胶质瘤仍然是最难治疗的实体瘤之一,部分原因在于肿瘤的高度血管化特性以及肿瘤内部存在更具抗性的干细胞样亚群。胶质瘤干细胞(GSCs)的维持需要细胞内以及更大的肿瘤微环境在信号传导和代谢方面发生特定改变。胶质瘤内的特定生态位有助于促进具有高致瘤性和高代谢可塑性的干细胞样亚群细胞的存活。了解这些维持途径以及生态位内的代谢依赖性,可能会为解决胶质瘤患者的肿瘤耐药性和复发问题指明潜在途径。