A narrative review of in vitro studies on the role of reactive oxygen species in aggravating high-grade serous ovarian cancer development
Ovarian cancer is often diagnosed at an advanced stage because its early symptoms are nonspecific, and the prognosis remains poor due to frequent recurrence and the development of drug resistance even after standard treatment. This review includes 19 in vitro studies and seeks to mechanistically summarize how reactive oxygen species (ROS) reinforce the tumorigenic program from the early stages of ovarian carcinogenesis to tumor progression, metastasis, and treatment resistance. Collectively, the selected studies suggest that exposure to environmental toxicants can increase ROS levels in ovarian epithelial cells, accompanied by inflammatory responses and elevated DNA damage markers, thereby creating a carcinogenesis-priming environment. During the progression stage, hypoxia, hormones, growth factors, and lipid signaling repeatedly activate survival and growth pathways, such as those involving HIF-1α/VEGF, JAK/STAT3, and AKT/mTOR, through ROS-mediated mechanisms to promote tumor cell proliferation, anti-apoptotic activity, and angiogenesis. In addition, ROS are associated with alterations in epithelial-to-mesenchymal transition-related markers, remodeling of the extracellular matrix, and regulation of matrix metalloproteinases, which enhance the metastatic and invasive potential of tumor cells. In the therapeutic context, ROS have been suggested to contribute to platinum-based chemotherapy resistance through mechanisms including changes in mitochondrial dynamics, activation of the DNA damage response, and reprogramming of ROS-dependent phosphorylation networks. Understanding the diverse molecular mechanisms and clinical manifestations associated with ROS expression in high-grade serous ovarian cancer (HGSOC) will contribute to a more precise understanding of its pathophysiology. Furthermore, studies on redox-targeted therapeutic strategies, particularly the application of mitochondria-targeted antioxidants, may provide valuable translational insights for the treatment of ovarian cancer and other ROS-related diseases.