Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers

Abstract Oxidative stress is a pathological condition of redox signaling dysregulation and macromolecular oxidative damage arising from elevated ROS levels. Oxidative stress interacts with tumor cell growth regulation and tumor microenvironment remodeling, and has been a critical hallmark of cancer. Targeting oxidative stress has garnered great attention in cancer therapy development. However, it is still challenging due to the complexity and heterogeneity of oxidative stress regulation across different cancers, and this encourages a comprehensive understanding of the oxidative stress network in cancers to overcome this obstacle. Therefore, we introduced the oxidative stress generation and regulatory network within tumor cells and discussed their roles in both tumor cells and the tumor microenvironment. Subsequently, we summarized the current therapeutic strategies and highlighted emerging clinical applications, providing an up-to-date overview of oxidative stress-based approaches. Particularly, their cross-application with immunotherapy and nanomedicine has provided an excellent opportunity to integrate multiple effects, exhibiting surpassing advantages. This review elaborates on oxidative stress in cancer biology and its therapeutic implications. By integrating current knowledge and the emerging coordination with immunotherapy and nanomedicine, we underscore the potential of oxidative stress-targeting approaches. Future research on overcoming therapeutic resistance and developing compatible platforms to combine multiple approaches will pave the way to cancer elimination.