DNA repair pathways in ovarian cancer: Implications for therapy and resistance

Ovarian cancer (OC) is the gynecological malignancy with the highest mortality, largely due to frequent resistance to conventional therapies. OC is characterized by high rates of genomic instability, often caused by DNA repair defects, and is commonly treated with platinum-based compounds and other genotoxic agents. Indeed, alterations in the DNA damage response (DDR), which are prevalent in many cancers, are particularly relevant in OC. Notably, homologous recombination deficiency is frequently observed, providing a rationale for strategies to enhance treatment efficacy by exploiting DNA repair defects. In this review, we examine the consequences of dysregulation and defects in the major DNA repair pathways in OC, with emphasis on their impact on therapy resistance, patient survival and OC risk. We also discuss current and emerging DDR-targeted therapies and highlight future directions for research aimed at improving clinical outcomes in OC.