Role of depression-mediated alterations in pro-inflammatory cytokines in carcinogenesis

Abstract

This review systematically examines the bidirectional relationship between MDD and cancer, establishing chronic inflammation—orchestrated primarily by IL - 6, TNF-α, and IL - 1β—as a critical biological link. It delineates the pathophysiological mechanisms through which depression activates the HPA axis, induces gut microbiota disruption, and provokes immune dysregulation, collectively fostering a systemic pro-inflammatory state. This state further potentiates oncogenesis via sustained activation of key signaling pathways—including JAK-STAT3, NF-κB, MAPK, and PI3K/AKT—that drive tumor proliferation, angiogenesis, immune evasion, and metastatic behavior. Although preclinical evidence is robust, clinical translation remains impeded by significant heterogeneity in inflammatory biomarkers—particularly IL - 1β—and a stark deficiency of rigorous interventional trials evaluating anti-cytokine biologics in cancer patients with comorbid depression. Future research must therefore advance beyond mechanistic inquiry toward inflammation-based patient stratification and prospective interventional studies, aiming to validate multimodal strategies targeting the depression-inflammation-cancer axis and ultimately propel psycho-oncology into an era of precision medicine.