On the Edge of Benefit and Harm: Reactive Oxygen Species in Cancer
TL;DR
A deeper understanding of tumor-specific redox vulnerabilities will be essential for developing precise and clinically effective ROS-oriented cancer therapies and the need for robust redox biomarkers is highlighted.
Abstract
Reactive oxygen species (ROS) are central regulators of cancer biology and represent a double-edged target in oncology. At physiological levels, ROS support signal transduction, proliferation, differentiation, and immune responses, whereas sustained ROS imbalance promotes DNA damage, genomic instability, metabolic reprogramming, and remodeling of the tumor microenvironment, thereby contributing to tumor initiation, progression, metastasis, and therapy resistance. Conversely, because many cancer cells operate close to the limit of tolerable oxidative stress, further ROS elevation can trigger apoptosis, ferroptosis, immunogenic cell death, and other cytotoxic programs. This review summarizes the major intracellular and microenvironmental sources of ROS, the mechanisms by which redox signaling shapes malignant transformation and tumor adaptation, and the antioxidant systems that buffer oxidative stress in cancer cells. We further discuss current therapeutic approaches based on both ROS suppression and ROS amplification, including redox-modulating small molecules, radiotherapy, photodynamic and sonodynamic therapy, catalytic nanomaterials, and ROS-responsive prodrugs and drug delivery systems. Particular attention is given to the context-dependent effects of ROS, the antioxidant paradox, tumor heterogeneity, hypoxia, off-target toxicity, and the need for robust redox biomarkers. A deeper understanding of tumor-specific redox vulnerabilities will be essential for developing precise and clinically effective ROS-oriented cancer therapies.