The role of circadian disruption, sleep dysregulation, lifestyle factors, and metabolic reprogramming in the pathogenesis and progression of ovarian cancer

Ovarian cancer remains one of the most lethal gynecologic malignancies, with high mortality due to late-stage diagnosis and limited effective treatments. Recent evidence highlights the importance of circadian rhythms, metabolic reprogramming, and lifestyle factors in shaping the initiation, progression, and treatment response of ovarian tumors. Disruption of the circadian clock, via genetic dysregulation or lifestyle behaviors such as night-shift work and poor sleep, has been associated with tumorigenesis, metabolic imbalance, and chemoresistance. Additionally, ovarian cancer cells demonstrate distinct metabolic adaptations, including enhanced glycolysis and glutaminolysis, supporting rapid proliferation and survival. Lifestyle factors such as diet, physical inactivity, obesity, and psychosocial stress further modulate cancer risk and therapeutic outcomes. This review synthesizes evidence on the molecular underpinnings of circadian and metabolic disruption in ovarian cancer and their interaction with modifiable behavioral factors. Furthermore, it explores emerging strategies such as chronotherapy and metabolic targeting to improve treatment efficacy and survivorship. The goal is to encourage a multidimensional perspective that integrates molecular biology with lifestyle medicine in the management of ovarian cancer.