Oxidative Stress in Cancer Therapy: Friend or Enemy?

Excessive cellular oxidative stress is widely perceived as a key factor in pathophysiological conditions and cancer development. Healthy cells use several mechanisms to maintain intracellular levels of reactive oxygen species (ROS) and overall redox homeostasis to avoid damage to DNA, proteins, and lipids. Cancer cells, in contrast, exhibit elevated ROS levels and upregulated protective antioxidant pathways. Counterintuitively, such elevated oxidative stress and enhanced antioxidant defence mechanisms in cancer cells provide a therapeutic opportunity for the development of drugs with different anticancer mechanisms of action (MoA). In this review, oxidative stress and the role of ROS in cells are described. The tumour-suppressive and tumour-promotive functions of ROS are discussed, and these two different therapeutic strategies (increasing or decreasing ROS to fight cancer) are compared. Clinically approved drugs with demonstrated oxidative stress anticancer MoAs are highlighted followed by description of examples of metal-based anticancer drug candidates causing oxidative stress in cancer cells via novel MoAs.