Understanding the mechanisms underlying obesity induced tumorigenesis: therapeutic perspectives to manage dysregulated lipid metabolism

Obesity has emerged as one of the most significant global public health challenges of the twenty-first century and is now firmly established as a major risk factor for multiple cancer types. Hypertrophic adipose tissue generates chronic low-grade inflammation, adipose hypoxia, and fibrosis, which leads to activation of IL-6/STAT3, NF-κB, and PI3K/Akt/mTOR signaling. Hyperinsulinemia and insulin resistance increase oncogenic pathways, while dysregulated adipokines by elevated leptin and reduced adiponectin enhance proliferation, angiogenesis, epithelial mesenchymal transition, and immune evasion. Obesity further remodels the tumor microenvironment by promoting extracellular matrix deposition, angiogenesis, immunosuppressive cell expansion, and metabolic competition that impairs antitumor immunity. Emerging evidence also implicates obesity-driven epigenetic reprogramming, altered microbiome composition, and metabolic heterogeneity as key determinants of tumor aggressiveness and treatment response. Conventional oncologic therapies rarely account for host metabolic status, which may contribute to variable therapeutic efficacy in obese patients. This review integrates mechanistic and translational evidence to define actionable vulnerabilities within obesity-induced tumorigenic pathways. We evaluate targeted metabolic interventions, cytokine blockade, adipokine modulation, immune checkpoint optimization, microbiome-directed strategies, and precision stratification frameworks. The present review outlines a multidimensional therapeutic roadmap to improve prevention, treatment response, and long-term outcomes in obesity-associated malignancies.