The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Ovarian Cancer: New Insight and Future Perspectives.
Ovarian cancer is a highly heterogeneous malignancy characterized by genetic diversity, clonal evolution, and therapeutic resistance, making it one of the deadliest gynecologic cancers worldwide. Neutrophil extracellular traps (NETs), composed of DNA, histones, and proteases, have emerged as critical mediators of tumor progression. This review comprehensively examines the interplay between neutrophils and ovarian cancer cells, emphasizing the role of NETs in shaping the tumor microenvironment and promoting disease progression. We critically analyze recent literature on the mechanisms by which NETs influence ovarian cancer metastasis, immune evasion, and chemoresistance. Furthermore, we discuss potential therapeutic strategies aimed at targeting NET formation to improve patient outcomes. NETs actively contribute to ovarian cancer progression by fostering a protumorigenic microenvironment, enhancing metastatic potential, and impeding the efficacy of standard therapies. Disrupting NET-associated pathways, including platelet-neutrophil interactions, represents a promising avenue for intervention. Emerging strategies, such as antiplatelet agents, have shown potential in modulating NET activity. However, their clinical application remains in early investigational stages, necessitating further research. This review underscores the pivotal role of NETs in ovarian cancer biology and highlights their potential as therapeutic targets. Although novel approaches, including antiplatelet agents, offer promising avenues for disrupting NET-driven tumor progression, their translational feasibility requires further validation. A deeper understanding of NET-mediated mechanisms could pave the way for innovative therapeutic strategies to enhance ovarian cancer treatment and improve patient survival.