Mini-reviewMetabolic regulation of glioma stem-like cells in the tumor micro-environment

- Tumor heterogeneity is a major obstacle in glioma treatment and is partly driven and promoted by glioma stem cells (GSCs).
- This heterogeneity constitutes not only genetic variability but also metabolic variability within a solid tumor.
- Metabolic plasticity of GSCs driven by intrinsic factors as well as extrinsic signaling from the glioma microenvironment.
- Therapeutic strategy targeting GSCs requires understanding of metabolic variation and crosstalk between the glioma and its microenvironment.

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.