The 5-Lipoxygenase Pathway in Ovarian Cancer: Mechanisms of Metastasis, Chemoresistance, and Translational Targeting

Ovarian cancer remains one of the most lethal gynecologic malignancies, characterized by early peritoneal dissemination, extensive microenvironmental remodeling, and frequent emergence of chemoresistance. Beyond genetic alterations, dysregulated lipid mediator signaling represents a regulatory layer that links inflammation, invasion, immune evasion, and cellular stress adaptation. The 5-lipoxygenase (5-LOX, encoded by ALOX5) pathway converts arachidonic acid into bioactive leukotrienes through coordinated activity with 5-LOX-activating protein (FLAP, encoded by ALOX5AP), thereby activating G protein-coupled receptors, including BLT1, BLT2, and cysteinyl leukotriene receptors. This narrative review synthesizes preclinical, translational, and clinical-association evidence for 5-LOX signaling in ovarian cancer. Particular attention is given to BLT2-driven invasion and chemoresistance, hypoxia-induced leukotriene production, macrophage recruitment, ALOX5AP-associated immune suppression, and biomarker-guided therapeutic development. The available evidence supports the 5-LOX axis as a biologically relevant but still clinically immature target. Future development should prioritize compartment-resolved pathway mapping, functional validation in patient-derived models and immune-competent experimental systems, and rational combination strategies rather than unselected monotherapy.