Dual Roles of Reactive Oxygen Species in Tumorigenesis and Therapeutic Targeting

Abstract

Reactive oxygen species (ROS) are integral to both the promotion and suppression of cancer. Acting as signaling molecules at physiological levels and as cytotoxic agents at high concentrations, ROS orchestrate complex interactions that define cancer initiation, progression, and therapeutic response. Understanding this duality is essential for developing precise redox-based cancer therapies. This review synthesizes current evidence on the multifaceted roles of ROS in carcinogenesis, tumor progression, and treatment, emphasizing redox-targeted therapeutic strategies that exploit oxidative vulnerabilities in cancer cells. A comprehensive literature search was conducted across several databases using the keywords “reactive oxygen species,” “oxidative stress,” “redox signaling,” “cancer therapy,” and “antioxidants.” Recent experimental and clinical studies were analyzed to integrate mechanistic insights and translational advances. ROS contribute to all phases of carcinogenesis through oxidative DNA damage, activation of oncogenic pathways (MAPK, PI3K/Akt/mTOR), and suppression of tumor suppressors such as p53. They promote epithelial–mesenchymal transition (EMT), angiogenesis, and immune evasion via redox-sensitive transcription factors (NF-κB, HIF-1α). Conversely, excessive ROS generation beyond the cellular antioxidant threshold induces apoptosis, providing a therapeutic avenue. Pro-oxidant approaches—including radiotherapy, photodynamic therapy, and chemodynamic nanotherapy—exploit this vulnerability, while antioxidant therapies protect normal tissues but risk diminishing treatment efficacy. Emerging combinatorial strategies integrating ROS modulation with immunotherapy and nanocarrier delivery offer enhanced selectivity and reduced toxicity. ROS stand at the crossroads of cancer pathogenesis and treatment. The future of redox oncology lies in precision modulation—achieving a therapeutic balance that selectively disrupts tumor homeostasis while preserving normal cell integrity. Personalized, biomarker-guided strategies targeting ROS dynamics hold the potential to revolutionize cancer therapy.