The Role of Oxidative Stress and Redox Regulation in Cancer

Oxidative stress is a pivotal regulator of cancer biology, influencing both the initiation and progression of malignancy. Oxidative stress results from an imbalance between the generation of reactive oxygen species (ROS) and the ability of antioxidant systems to detoxify them. While physiological levels of ROS are essential for cellular homeostasis, excessive ROS can damage DNA, proteins, and lipids, leading to cellular death. Paradoxically, cancer cells rely on moderately elevated ROS levels to sustain proliferative signaling, metabolic reprogramming, and invasion. To prevent oxidative damage, they rewire their redox networks by simultaneously increasing ROS production and enhancing antioxidant defense lines. Meanwhile, cancer stem cells (CSCs) keep even tighter redox control by preserving intrinsically low ROS levels through metabolic adaptation and robust antioxidant capacity. Elevated ROS not only promotes tumor growth but also modulates the tumor microenvironment (TME), inducing immune evasion, epithelial-mesenchymal transition, and therapy resistance. Clinically, targeting redox balance has become a promising approach for cancer diagnosis and treatment. This Chapter is dedicated to provide a practical summary of current knowledge on oxidative stress in cancer cells and how it contributes to cancer formation and progression.