Redox tolerance and metabolic reprogramming in solid tumors.

Abstract

Tumor cells needto cope with the host environment forsurvival and keep growing in hard conditions. This suggeststhat tumors must acquire characteristics more potent than what isseen 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 suggeststhat 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 suggeststhe 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 fibroblastswith 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.