The microbiome and ovarian cancer: insights, implications, and therapeutic opportunities

Ovarian cancer is the leading cause of gynecologic cancer death in the United States. Most ovarian cancer patients are diagnosed with advanced-stage disease, which poses a challenge for early detection and effective treatment. At present, cytoreductive surgery and platinum-based chemotherapy are foundational for patients with newly diagnosed ovarian cancer, but unfortunately, most patients will recur and die of their disease. Therefore, there is a significant need to seek innovative, novel approaches for early detection and to overcome chemoresistance for ovarian cancer patients. The microbiome, comprising diverse microbial communities inhabiting various body sites, is vital in maintaining human health. Changes to the diversity and composition of the microbial communities impact the microbiota-host relationship and are linked to diseases, including cancer. The microbiome contributes to carcinogenesis through various mechanisms, including altered host immune response, modulation of DNA repair, upregulation of pro-inflammatory pathways, altered gene expression, and dysregulated estrogen metabolism. Translational and clinical studies have demonstrated that specific microbes contribute to ovarian cancer development and impact chemotherapy's efficacy. The microbiome is malleable and can be altered through different approaches, including diet, exercise, medications, and fecal microbiota transplantation. This review provides an overview of the current literature regarding ovarian cancer and the microbiome of female reproductive and gastrointestinal tracts, focusing on mechanisms of carcinogenesis and options for modulating the microbiota for cancer prevention and treatment. Advancing our understanding of the complex relationship between the microbiome and ovarian cancer may provide a novel approach for prevention and therapeutic modulation in the future.