ROS homeostasis and metabolism: a critical liaison for cancer therapy

Evidence indicates that hypoxia and oxidative stress can control metabolic reprogramming of cancer cells and other cells in tumor microenvironments and that the reprogrammed metabolic pathways in cancer tissue can also alter the redox balance. Thus, important steps toward developing novel cancer therapy approaches would be to identify and modulate critical biochemical nodes that are deregulated in cancer metabolism and determine if the therapeutic efficiency can be influenced by changes in redox homeostasis in cancer tissues. In this review, we will explore the molecular mechanisms responsible for the metabolic reprogramming of tumor microenvironments, the functional modulation of which may disrupt the effects of or may be disrupted by redox homeostasis modulating cancer therapy. Oxygen is vital for life but also poses risks due to various reactive oxygen species that can cause damage associated with diseases and aging. Cancer cells can be susceptible to increased reactive oxygen species. Changes in the metabolism of cancer cells related to the balance between oxidant and antioxidant levels may be responsible for resistance to cancer therapy and study of the mechanisms may offer new targets for treatment. Researchers in South Korea led by Jaehong Kim at Gachon University and Jong-Sup Bae at Kyungpook National University review understanding of the molecular mechanisms of metabolic reprograming that alter the balance between oxidant and antioxidant levels in cancer cells. They highlight a lack of evidence relevant to human patients, as opposed to cultured cells. The therapeutic possibilities of drugs that could change the balance deserve further exploration.