Obesity, sleep apnea and cancer revisited.

Obstructive sleep apnea (OSA), obesity, and cancer constitute an interconnected pathophysiological triad withi mportant implications for morbidity and mortality. Obesity is a major upstream driver of both OSA and tumorigenesis, while OSA contributes independently through intermittent hypoxia, sleep fragmentation, systemici nflammation, oxidative stress, immune dysregulation, and sympathetic activation. Emerging evidence links OSA-associated hypoxemia to cancer initiation, progression, and treatment response, with hypoxic burden and nocturnal oxygen desaturation metrics outperforming the apnea-hypopnea index in predicting cancer-related outcomes. Mechanistic advances implicate immune checkpoint signaling, extracellular matrix remodeling, and metabolic-hepatic pathways as key mediators of OSA-related oncogenesis. Epidemiological studies support associations between OSA and several malignancies independent of obesity, although residual confounding remains a challenge. Therapeutically, continuous positive airway pressure may mitigate hypoxemia-related pathways, whereas bariatric surgery and GLP-1/GIP receptor agonists off er the potential to simultaneously reduce obesity, OSA severity, and cancer risk. Precision medicine approaches integrating hypoxemia phenotyping, immune profi ling, and targeted interventions are needed to optimize prevention and treatment strategies.