Chapter 1 - Epithelial ovarian cancer: Genomic landscape and evolving precision treatment

Abstract

Ovarian cancer management has undergone a transformation over the past decade, with a greater understanding of tumor biology, elucidation of novel targets for therapeutic intervention, and better recognition of the role of genetic predisposition genes in response to treatment. For more than 20years, cytoreductive surgery and the combination of a platinum agent and a taxane has served as the primary treatment strategy. The antiangiogenic agent bevacizumab has been shown to be clinically active when added to chemotherapy and delivered as a “maintenance” strategy in the front-line for high-risk disease. However, ovarian cancer is not a single disease and can be subdivided into multiple histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features, and treatments. Poly-(ADP-ribose) polymerase (PARP) inhibitors are currently utilized as single-agent “second-line” treatment options, or in the maintenance setting in women with BRCA mutation-associated subtypes, and recent promising trial results are likely to see PARP inhibitors used in the maintenance therapy in the front-line, at least for women carrying a BRCA mutation. Despite these improvements, disease relapse still occurs in a majority of patients with advanced epithelial ovarian cancer. Multiple single agent and combination therapy strategies have been delivered in the relapse setting with the goal to prolong survival and optimize quality of life. Current clinical research efforts in ovarian cancer focus on the potential role of immune-checkpoint inhibitors, or immune modulation, used alone or in combination with PARP inhibitors or antiangiogenic agents. Understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study and are essential to improving outcomes in ovarian cancer.