Precision redox oncology: Exploiting antioxidant dependencies and oxidative vulnerabilities in cancer

Redox biology has emerged as a central driver of cancer initiation, metabolic reprogramming, immune evasion, and therapeutic resistance. Tumor cells exist in a chronically oxidative environment but maintain survival by upregulating antioxidant systems, thereby sustaining a narrow “ROS window” that supports proliferation while preventing lethal oxidative damage. Within this window, reactive oxygen species function as signaling mediators that promote oncogenic pathways and tumor progression. Antioxidant systems exhibit context-dependent roles: while they suppress early carcinogenesis, they are frequently co-opted in established tumors to support progression, ferroptosis resistance, and therapy failure, a phenomenon referred to as the antioxidant paradox. Emerging evidence also suggests that exogenous antioxidants may, in certain contexts, impair the efficacy of ROS-dependent therapies. However, significant challenges remain, including the lack of reliable methods to monitor redox dynamics in vivo, limited understanding of tumor-specific redox dependencies, and the redundancy of antioxidant networks that drive therapeutic resistance. This review integrates mechanistic, preclinical, and clinical insights to define the framework of precision redox oncology. We highlight how redox-dependent signaling and antioxidant adaptation create therapeutic vulnerabilities and discuss strategies to exploit these processes. Future progress will require biomarker-driven patient stratification, development of combination therapies targeting multiple redox pathways, and advanced tools for real-time redox assessment to enable more effective and personalized cancer treatment.