Biological Pathways that Link Cancer and Major Depressive Disorders

Cancer is widely recognized as a physical disease, but it can also have significant effects on mental health. Approximately 15–25% of cancer patients experience major depressive disorder (MDD) or clinically significant depressive symptoms, suggesting that depression is more than an emotional response to a cancer diagnosis. Growing evidence indicates that chronic inflammation and immune activation may contribute to cancer-related depression, although the biological mechanisms underlying this relationship are not yet fully understood. This review examines the inflammatory pathway linking cancer and depression, with a particular focus on chronic inflammation, immune activation, inflammatory biomarkers, and their effects on brain function. Current evidence suggests that inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP), may influence neurotransmitter signaling and contribute to depressive symptoms through multiple biological mechanisms. However, most available evidence remains observational, making it difficult to establish a direct relationship between inflammation and depression. Overall, this review supports the biopsychosocial model by demonstrating that biological, psychological, and social factors likely interact to influence depression in cancer patients. A better understanding of these mechanisms may improve the recognition and management of depression while guiding future research and more personalized approaches to cancer care.