Bidirectional relationship between cancer and depression: From shared mechanisms to integrated therapeutic strategies

Cancer and depression exhibit a clinically significant bidirectional association, as evidenced by the key findings: cancer patients are prone to depression, and depressed patients are prone to cancer. This may help explain why depression is commonly observed in cancer populations, where it is associated with poorer treatment adherence, diminished quality of life, and elevated mortality. Conversely, depression associated with an elevated cancer risk, potentially mediated by factors, such as neuroimmune dysregulation, chronic inflammation, and unhealthy lifestyles. Shared mechanisms include stress-induced β-adrenergic signaling, neuroinflammation, kynurenine pathway activation, and gut-brain-tumor axis disruptions involving bacterial metabolites like acetate. Common lifestyle factors such as smoking and sleep disruption, may further link both conditions through pathways like Wnt/β-catenin and JAK/STAT. Integrated treatment strategies combining anti-inflammatory medications such as non-steroidal anti-inflammatory drugs (NSAIDs) or tumor necrosis factor-α (TNF-α) inhibitors, psychotropic medications such as selective serotonin reuptake inhibitors (SSRIs), lifestyle modifications (e.g., exercise, Mediterranean diet) and psychotherapy (e.g., CBT) are promising for breaking the potential depression-cancer cycle and improving outcomes.