Loss of effective DNA repair correlates with carcinogenesis; conversely, an upregulation of DNA repair is often seen in cancer cells in response to DNA-damaging agents such as platinum-based chemotherapy and radiation. The capacity of cancer cells to identify and repair the damage caused by therapeutic assault is a major driver of acquired resistance and therefore limits the effectiveness of these conventional treatment approaches. Therefore, pharmacological targeting of DNA repair proteins may increase the efficacy of current treatments and overcome the risk of therapeutic resistance. Furthermore, the concept of synthetic lethality, whereby loss of function of either one of two interrelated genes is not lethal but loss of both genes results in cell death, provides a promising platform for pharmacological targeting of DNA repair genes. Endonucleases are enzymes, which are involved in several DNA repair pathways and act to cleave either damaged DNA or nucleotide by-products of repair, thus facilitating progression to DNA synthesis and ligation.[1]