Preventive Strategies in Epithelial Ovarian Cancer

Abstract

Despite advances in surgery and chemotherapy, epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy 1. Due to lack of a specific prodromal symptomatology as well as effective screening strategies, the vast majority of EOC patients present with advanced stage disease will ultimately die from their disease 1. Furthermore, while up to 80% of patients will respond to conventional primary platinum/taxane chemotherapy, greater than 60% will experience disease recurrence, and current reports indicate discouraging response rates of 20% in women with resistance to platinum-based chemotherapy 2. Preventive strategies, including improvements in early detection of disease as well as in preventing disease recurrence, are, therefore, crucial to improving prognosis. Ovarian cancer prevention can be defined by two main strategies: 1) early detection of cancer in at-risk patients and 2) prevention of recurrent disease in patients with an established diagnosis of cancer. Through the use of screening tools, such as serum biomarkers and medical imaging, early disease detection offers the promise of identifying cancer while still localized and potentially curable 3. Secondary preventive approaches aim to maintain patients without evidence of active disease and thereby extend their disease-free survival. Surveillance methods including serial biomarker measurements as well as therapeutic vaccinations have been examined for their impact on survival outcomes. Finally, risk stratification is critical to the success of any cancer prevention strategy; capitalizing on risk-reducing behaviors and intensive screening is most likely to improve individuals at greatest risk for disease-related morbidity and mortality. Current research in the early detection of ovarian cancer largely focuses on biomarker discovery, using transcriptome analysis, proteomics, epigenomics, metabolomics and glycomics of differentially expressed molecules between women with disease and healthy controls. Biomarkers already approved by the FDA (i.e., CA125 and HE4) or those under investigation, including osteopontin, MUC1 and mesothelin, offer hope for women at risk for disease development, especially those with predisposing genetic mutations 4. As part of this effort, we have generated site-specific biotinylated recombinant antibodies secreted by yeast (Biobodies 5) to costand time-effectively generate antibodies for developing screening tools for large populations of women 6. In addition, biomarkers, especially tumor associated antigens, may also serve as targets for vaccination 7.