Genetic approaches for targeted oxidative stress

Cancer cells display dysregulated metabolic programs, which result in excessive reactive oxygen species (ROS) leading to oxidative stress. ROS reaction with macromolecules, including proteins, lipids, and nucleic acids, can result in damaging modifications with alter or nullify function. While tumors upregulate antioxidant defences for viability, they remain sensitive to additional oxidant perturbations. Because of this, therapies that overwhelm cancers with ROS are gaining clinical attention due to their potential targeting of diseased tissue over normal tissue. In this review, we summarize the available genetic tools for targeted ROS production in both cellular and organismal models, specifically focusing on tools with spatial and temporal control. Largely, these approaches use light to activate a chromophore in the cell, which produces ROS for protein inactivation, DNA damage, or cell ablation. These photosensitizers are genetically fused to target proteins of interest, and all have advantages and disadvantages for both basic and translational research, which we discuss below.