Abstract
Ovarian cancer remains the most lethal malignancy of the female reproductive tract. Because early-stage disease is almost silent, roughly 70% of patients present with advanced, disseminated tumors. The current standard-maximal cytoreductive surgery followed by platinum-based chemotherapy-achieves only transient control: recurrence is the rule rather than the exception, and acquired resistance steadily erodes therapeutic benefit. A growing body of evidence now positions vascular endothelial growth factor (VEGF) at the epicenter of this therapeutic impasse. Beyond driving neo-angiogenesis, VEGF fuels invasion, metastatic spread, and chemoresistance and independently predicts malignant ascites formation. Exploiting this insight, VEGF-directed molecular therapeutics and immunotherapies are emerging as a rational strategy to break past the plateau of conventional treatment. By dissecting and re-engineering the tumor vasculature, these approaches offer the prospect of precision regimens that restore drug sensitivity and prolong survival. Here we synthesize current knowledge on VEGF signaling in ovarian cancer. We catalogue upstream regulators of VEGF expression within the tumor microenvironment, delineate the downstream pathways that orchestrate malignant behavior, and critically review VEGF-targeted agents that have entered-or are poised to enter-the clinic.