CHRONIC STRESS AND CANCER PROGRESSION: NEUROENDOCRINE–IMMUNE MECHANISMS AND IMPLICATIONS FOR ANTICANCER THERAPY

Abstract

Chronic stress is increasingly regarded as a biologically active modifier of cancer progression rather than solely a psychological consequence of malignant disease. Persistent activation of the hypothalamic -pituitary-adrenal axis and sympathetic nervous system results in prolonged glucocorticoid and catecholamine signaling capable of affecting tumor cells, stromal components, and immune populations. Experimental and translational evidence indicates that chronic stress may promote tumor-cell survival and plasticity, angiogenesis, invasion, metastatic dissemination, remodeling of the tumor microenvironment, and suppression of antitumor immunity. Key mechanisms include stress -associated reprogramming of tumor -associated macrophages, m yeloid-derived suppressor cells and neutrophils, formation of neutrophil extracellular traps, and dysfunction or exhaustion of cytotoxic T lymphocytes and natural killer cells. These mechanisms may also contribute to reduced sensitivity to chemotherapy, targeted therapy, and immune checkpoint blockade. Pharmacological targeting of beta -adrenergic signaling remains investigational as a general anticancer strategy, whereas glucocorticoid receptor antagonism has demonstrated clinical benefit in a specific treatment -resistant tumor setting. Psycho - oncological interventions, physical activity, and comprehensive supportive care have an established role in improving patient -reported and functional outcomes. Further prospective biomarker-driven studies are required to determine whether modification of stress-related pathways can improve anticancer treatment outcomes.