Chronic stress-related neuroendocrine mediators and ovarian cancer

Ovarian cancer (OC), as one of the three major gynecological tumors, has been known as the "silent killer". It is characterized by high mortality, high recurrence rate, and frequent drug resistance. Chronic stress has been increasingly recognized as a potential contributor to ovarian cancer progression through dysregulation of neuroendocrine pathways, particularly via the prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). Key mediators, including glucocorticoids (GCs), catecholamines (epinephrine (E), norepinephrine (NE), and dopamine (DA)), and other neuroendocrine factors, contribute to tumor progression by modulating cell proliferation, metastasis, angiogenesis, chemoresistance, and tumor immune microenvironment. This review summarizes current evidence on the role of neuroendocrine mediators in ovarian cancer progression, highlighting molecular mechanisms, clinical and preclinical findings, and potential therapeutic strategies. Understanding neuroendocrine-ovarian cancer crosstalk may provide novel insights into ovarian cancer progression and inform combinatorial therapies targeting stress-mediated tumorigenesis.