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Chronic psychological stress (CPS) manifests as sustained dysregulation arising from prolonged adaptive responses to chronic endogenous and exogenous stimuli. Clinical evidence indicates that CPS markedly influences cancer progression, with most oncology patients developing detectable stress-related psychological disorders during disease management. This review synthesizes recent advances in understanding CPS-mediated oncogenic mechanisms and evaluates current intervention approaches. Mechanistically, CPS compromises immune surveillance through neuroendocrine-mediated hormonal dysregulation, impairing malignant cell recognition and clearance. Concurrently, CPS hormones promote tumor metabolic adaptation via hypothalamic\u2013pituitary\u2013adrenal axis-driven metabolic reprogramming, enhancing glycolytic flux to support uncontrolled proliferation. CPS further accelerates tumor progression through reactive oxygen species-induced mitochondrial impairment, DNA damage accumulation, and inflammatory cascades. Notably, CPS induces gut microbiota perturbations that reciprocally amplify tumorigenic processes through microbial metabolite disturbances and neuroimmune crosstalk, creating a self-perpetuating pathogenic loop. Therapeutic strategies to address cancer-related CPS that encompass pharmacological agents targeting neuroendocrine pathways, psychosomatic behavioral interventions, social environment adjustments, and evidence-based traditional Chinese medicine formulations demonstrate potential in cancer prevention, treatment, and outcome optimization. However, challenges remain in achieving precise neuromodulation and minimizing intervention side effects, underscoring the need for mechanism-guided therapeutic innovations.<\/jats:p>","DOI":"10.34133\/research.0948","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T13:37:23Z","timestamp":1758893843000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":32,"title":["Chronic Psychological Stress in Oncogenesis: Multisystem Crosstalk and Multimodal Interventions"],"prefix":"10.34133","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6668-4885","authenticated-orcid":false,"given":"Bin","family":"Huang","sequence":"first","affiliation":[{"name":"The Affiliated People\u2019s Hospital of Fujian University of Traditional Chinese Medicine","place":["China"]},{"name":"Academy of Integrative Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatrics, \rFujian University of 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