Targeting DNA repair pathways: mechanisms and potential applications in cancer therapy

Abstract

DNA damage can be caused by both endogenous and environmental factors, such as replication errors, reactive oxygen species (ROS) and chemotherapeutic drugs. Accurate and effective repair of DNA damage can preserve the integrity of the genome. However, if left unrepaired or repaired inappropriately, DNA damage could lead to the development of a variety of diseases, including cancers. DNA damage response (DDR) pathways are regarded as attractive tumor therapeutic targets. In recent years, representative drugs like poly(ADP-ribose) (PAR) polymerase inhibitors (PARPis) target DNA damage repair pathways and thus have generated profound breakthroughs in the treatment of tumors. Therefore, it is necessary to understand the mechanisms behind these drugs for treating tumors. In this review, we will discuss the mechanisms of representative tumor therapeutic drugs in the field of DNA damage repair and our current understanding of the related inhibitors that are expected to be used in future cancer therapies. We believe that these underlying mechanisms will provide significant support for directing drug use and future drug development.