Redox tolerance and metabolic reprogramming in solid tumors.

Tumor cells need to cope with the host environment for survival and keep growing in hard conditions. This suggests that tumors must acquire characteristics more potent than what is seen for normal tissue cells, without which they are condemned to disruption.  For example, cancer cells have more potent redox tolerance compared with normal cells, which is due to their high adaptation to an oxidative crisis. In addition, increased demand for bioenergetics and biosynthesis can cause a rise in nutrient uptake in tumors. Utilizing nutrients in low nutrient conditions suggests that tumors are also equipped with adaptive metabolic processes. Switching the metabolic demands toward glucose consumption upon exposure to the hypoxic tumor microenvironment, or changing toward using other sources when there is an overconsumption of glucose in the tumor area are examples of fitness metabolic systems in tumors. In fact, cancer cells in cooperation with their nearby stroma (in a process called metabolic coupling) can reprogram their metabolic systems in their favor. This suggests the high importance of stroma for meeting the metabolic demands of a growing tumor, an example in this context is the metabolic symbiosis between cancer-associated fibroblasts with cancer cells. The point is that redox tolerance and metabolic reprogramming are interrelated, and that, without a doubt, disruption of redox tolerance systems by transient exposure to either oxidative or antioxidative loading, or targeting metabolic rewiring by modulation of tumor glucose availability, controlling tumor/stroma interactions, etc. can be effective from a therapeutic standpoint.