Reductive Stress, Bioactive Compounds, Redox-Active Metals, and Dormant Tumor Cell Biology to Develop Redox-Based Tools for the Treatment of Cancer.

Significance: Cancer is related to redox biology from many points of view, such as initiation and promotion, metabolism and growth, invasion and metastasis, vascularization, or through the interaction with the immune system. In addition, this extremely complex relationship depends on the redox homeostasis of each cellular compartment, which might be used to fight cancer. Recent Advances: New ways of modulating specific and little explored aspects of redox biology have been revealed, as well as new delivery methods or uses of previously known treatments against cancer. Here, we review the latest experimental evidence regarding redox biology in cancer treatment and analyze its potential impact in the development of improved and more effective antineoplastic therapies. Critical Issues: A critical issue that deserves particular attention is the understanding that both extremes of redox biology (i.e., oxidative stress [OS] and reductive stress) might be useful or harmful in relation to cancer prevention and treatment. Future Directions: Additional research is needed to understand how to selectively induce reductive or OS adequately to avoid cancer proliferation or to induce cancer cell death.