Adipokines Reframing the Obesity Paradox in Precision Oncology

Abstract

The increasing coexistence of obesity, insulin resistance, and malignancy has intensified interest in ad-ipokines as mechanistic links between metabolic disease and tumor progression. This review summarizes tumor-specific evidence in breast, colorectal, endometrial, ovarian, and hepatocellular cancers and discusses the biomarker and therapeutic value of circulating adipokines, receptor antagonists, pathway modulators, and metabolism-informed combination strategies. To date, adipokines are bioactive mediators released by adipocytes, stromal cells, and immune cells within adipose depots and tumor-adjacent fat. Rather than acting as isolated biomarkers, they form a dynamic signaling network that regulates proliferation, apoptosis resistance, angiogenesis, epithelial-mesenchymal transition, cancer stem-like behavior, and immune remodeling. Leptin, resistin, visfatin, and chemerin are predominantly associated with pro-tumorigenic effects, whereas adiponectin and omentin are more often linked to anti-inflammatory and anti-proliferative actions. Emerging adipokines such as apelin, vaspin, irisin, and RBP4 (Retinol-binding protein 4) display context-dependent behavior that varies with tumor type, receptor expression, and metabolic state. Mechanistically, adipokines converge on JAK(Janus kinase)/STAT, PI3K (Phosphoinositide 3-kinase)/Akt/mTOR (Mechanistic target of rapamycin), MAPK/ERK (Mitogen-activated protein kinase / Extracellular signal-regulated kinase), AMPK (AMP-activated protein kinase), NF-kB, and insulin/IGF-1 pathways, thereby influencing both tumor cells and the surrounding micro-environment. The data suggest that precision oncology could be improved by integrating adipokine biology into patient stratification strategies, especially for metabolically dysregulated populations in whom tumor behavior and treatment response are shaped by the endocrine and immune state of adipose tissue.