These novel findings indicate that the targeted covalent inhibition of cellular redox regulators, such as thioredoxin reductases, warrants further research and could be employed to extend the use of PARP-trapping small molecules to HR-proficient, p53 wildtype cancers that exhibit a high basal level of ROS and/or an intrinsic susceptibility to replication stress. Here, PRDX5 is linked to cancer.