Obesity as a Systems‐Level Driver of Cancer: Mechanisms and Nutritional Reprogramming

Obesity has emerged as a global health crisis and a potent driver of cancer incidence and mortality, yet its mechanistic impact on tumor biology remains underappreciated. Far from being a passive risk factor, obesity acts as a systems-level oncogenic stressor, reshaping hormonal signaling, immunometabolism, and epigenetic stability across the body. This review synthesizes current knowledge on the physiological, cellular, and molecular cascades linking obesity to carcinogenesis, with emphasis on chronic inflammation, metabolic reprogramming, tumor microenvironment remodeling, and microbiome dysbiosis. We also examine how dietary patterns modulate these cancer-associated processes, positioning nutrition not merely as a preventive tool but as a programmable interphase with cancer biology through soft epigenetic reprogramming. Emerging frameworks in precision nutritional oncology, driven by nutrigenomics, metabolomics, and patient-specific molecular profiling, offer promising avenues for personalized cancer prevention and metabolic targeting. By integrating epidemiological trends, mechanistic insights, and translational strategies, we propose a paradigm shift: treating obesity not just as a comorbid risk factor but also as a modifiable oncogenic ecosystem-one that can be reprogrammed through informed, individualized precision dietary interventions.