Therapeutic upregulation of DNA repair pathways: strategies and small molecule activators

DNA repair activity diminishes with age and genetic mutations, leading to a significantly increased risk of cancer and other diseases. Upregulating the DNA repair system has emerged as a potential strategy to mitigate disease susceptibility while minimizing cytotoxic side effects. However, enhancing DNA repair activity presents significant challenges due to the inherent inefficiency in activator screening processes. Additionally, pinpointing a critical target that can effectively upregulate overall repair processes is complicated as the available information is somewhat sporadic. In this review, we discuss potential therapeutic targets for upregulating DNA repair pathways, along with the chemical structures and properties of reported small-molecule activators. We also elaborate on the diverse mechanisms by which these targets modulate repair activity, highlighting the critical need for a comprehensive understanding to guide the development of more effective therapeutic strategies.