DNA Repair–Based Mechanisms of Platinum Resistance in Epithelial Ovarian Cancer: From Bench to Bedside

Platinum-based chemotherapy constitutes the mainstay systemic treatment for patients with epithelial ovarian cancer (EOC). Significant and durable clinical responses are achieved when platinum is administered along with taxanes after debulking surgery, but relapses are common in advanced disease within 2 years upon completion of primary therapy. Furthermore, between 20% and 30% of patients will never respond or will progress shortly after finishing the platinum-containing regimen. To avoid unnecessary toxicities, ideally physicians should be capable of selecting which patients might benefit the most from a particular treatment based on established, predictive factors. Although the cytotoxicity of cisplatin is well described, the mechanisms of platinum resistance developed by tumoral cells are not so well understood. Changes in the DNA repair pathways in tumors possibly have an important role in the development of its platinum-resistant phenotype. Recent advances in this area have identified potential biomarkers (eg, ERCC1 mRNA and protein expression and BRCA mutational status) that may correlate with the clinical efficacy of a platinum-based chemotherapy. Clinical studies that evaluate its potential application in the management of patients with ovarian cancer are now emerging. Future validation of these predictive biomarkers of response to platinum, as well as to other chemotherapeutic agents (eg, taxanes), might set the stage for a more biology-based and rational therapeutic approach to advanced EOC. We review the most recent advances in translational research regarding the DNA repair pathways as a potential source for describing and validating biomarkers of response to platinum agents in ovarian cancer.