Abstract
Breast and ovarian cancers (BC and OC) remain among the leading causes of cancer-related deaths among women worldwide. Their progression is critically dependent on tumor angiogenesis and a permissive metabolic microenvironment. Vascular endothelial growth factor (VEGF) is a key factor in tumor angiogenesis and neovascularization. Leptin, conversely, a hormone that is produced by adipocytes, serves as an important mediator of tumor proliferation, inflammation, and metastasis. Increasing evidence suggests that VEGF and leptin act via multiple overlapping oncogenic pathways. They collectively promote tumor growth, survival, and angiogenesis. Obesity, hypoxia, and interactions between adipose tissue and the stroma further enhance this oncogenic axis by increasing the expression of VEGF and leptin and supporting metabolic reprogramming of the tumor. In BC and OC, persistent activation of the VEGF-leptin network contributes to aggressive disease progression, treatment resistance, and unfavorable clinical outcomes. Studies have indicated cytokine release, hypoxia and necrosis induction, angiogenesis, and tumor metastasis by interconnected immune pathways mediated by leptin and VEGF. Important roles of different receptors have also been uncovered in several in-vitro and in-vivo experiments. The findings have opened avenues for developing targeted monotherapies and combination therapeutic strategies to control tumor progression by inhibiting diverse signaling pathways. This review highlights the reciprocal VEGF-leptin feedback interaction in obesity-associated BC and OC, integrating evidence form biomarker studies and therapeutic perspectives. It also examines the influence of obesity and hypoxia on tumor progression and discusses current therapeutic strategies targeting this interconnected angiogenic-metabolic interaction.