Cell Biol Int. 2020 Nov 25.
Tumor cells are needed to cope with the host environment in order to maintain their survival and keep growing in hard conditions. This infers that tumors must acquire characteristics more potent than what seen for normal tissue cells, without which they are condemned to disruption. As for example, cancer cells have more potent redox tolerance compared to normal cells, which is due to their high adaptation to the oxidative crisis. In addition, increased demand for bioenergetics and biosynthesis can cause a rise of nutrient uptake in tumors. Utilizing nutrients in low nutrient conditions infers that tumors are also equipped with adaptive metabolic processes. Switching the metabolic demands toward glucose consumption upon exposure to the hypoxic TME, or changing toward using other sources when there is an over-consumption 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 infers 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 (CAFs) with cancer cells. The point is that redox tolerance and metabolic reprogramming are inter-related, 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 therapeutic window. This article is protected by copyright. All rights reserved.
Keywords: cancer; glycolysis; hallmark; normal cell, mitochondria; oxidative stress; reprogramming; tumor microenvironment (TME)