Redox processes in the treatment of advanced skin cancers.

Reactive oxygen and nitrogen species (ROS/RNS) are central regulators of cellular processes, governing signaling, metabolism, and stress responses. The source of reactive species, together with the capacity of antioxidant networks, determines whether redox signals support cell survival or provoke cytotoxicity. Dysregulation of redox homeostasis promotes genomic instability, metabolic reprogramming, immune evasion, and therapy resistance, thereby contributing to tumor initiation and progression. Tumors further adapt their metabolism and antioxidant defenses, which changes their sensitivity to oxidative stress. Consequently, redox biology emerges as a highly promising target for intervention. This review focuses on topical ROS‑based strategies for advanced skin cancer, offering an overview of fundamental redox principles and evaluating both conventional topical agents (e.g., 5‑fluorouracil and imiquimod) and direct ROS-producing modalities (e.g., photodynamic therapy and medical gas plasma). Topical ROS‑based interventions can impose defined oxidative stress on tumors, combining direct tumoricidal activity with immunogenic effects. While standard agents rely primarily on antiproliferative or immune‑stimulatory mechanisms, pro‑oxidant therapies intentionally generate ROS/RNS to induce tumor cell death and stimulate antitumor immunity. They therefore may synergize with drugs that impair antioxidant defenses or sensitize cells to ferroptosis. Advanced cutaneous malignancies are suited to topical redox interventions because their surface accessibility permits localized treatment that addresses unmet therapeutic needs. To translate these opportunities, harmonized delivery and dosimetry, validated biomarkers for tumor redox phenotypes, and prospective trials integrating pharmacodynamic and safety endpoints are required to guide patient selection and combination strategies.