Reactive oxygen species and cancer

Reactive oxygen species (ROS) were once considered only as a toxic by-product of aerobic metabolism. Many studies done in the past several decades, however, revealed that ROS have necessary physiological and pathological functions. In the context of cancer, there has been a persistent interest in whether ROS have a tumor-supportive or a tumor-suppressive role. Hydrogen peroxide (H₂O₂) conducts signaling pathways essential for the survival, proliferation, and metastasis of cancer cells. H₂O₂, however, can also induce the production of cytotoxic lipid ROS and trigger cancer cell death, such as ferroptosis. As a result, cancer cells increase not only the rate of H₂O₂ production to hyperactivate the protumorigenic signaling but also their antioxidant capacity to evade the lipid ROS-induced cell death. This unique reliance of cancer cells on both the pro- and antioxidative capacities may provide opportunities to specifically target them via ROS manipulation. In this chapter, we review the major findings that lead to the current understanding of the redox environment in cancer cells and the strategies of redox therapies against cancer.