Can Chronic Stress Influence Cancer Progression?

Chronic stress may influence biological pathways involved in tumor progression, although its effects vary by cancer type and the available evidence is largely associative. Recent reviews examined the neuroendocrine and neuroimmune mechanisms involved, pharmacologic approaches under investigation, and the role of psychological care in improving patients’ quality of life and clinical outcomes.A systematic review reported that chronic stress is associated with prolonged activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. This response is accompanied by increased release of catecholamines (epinephrine and norepinephrine) and glucocorticoids (primarily cortisol). These mediators can influence immune function and the tumor microenvironment.According to the researchers, these mechanisms are associated with a decrease in antitumor immune surveillance, increased inflammation and oxidative stress, and activation of signaling pathways involved in cancer cell proliferation and survival. However, the available evidence is largely associative and does not establish a direct causal relationship between psychological stress and tumor progression.Effects Vary by Cancer TypeThe authors of the review distinguished cancers associated with relatively high survival rates, such as breast and prostate cancer, from those with less favorable prognoses, including pancreatic and ovarian cancer. Although they organized their analysis according to tumor prognosis, this approach allowed them to compare mechanisms associated with chronic stress across different cancer types.The authors identified the following processes in relation to each tumor site:Breast cancer. Activation of beta-adrenergic pathways that promote tumor growth, angiogenesis, metastasis, and certain forms of treatment resistance.Prostate cancer. Activation of antiapoptotic mechanisms and pathways involved in tumor progression, with a possible reduction in sensitivity to hormone therapy reported in some experimental models.Pancreatic cancer. Activation of inflammatory mechanisms, particularly those involving interleukin-6, which may contribute to tumor progression and depressive symptoms often observed in these patients.Ovarian cancer. Increased levels of inflammatory and proangiogenic mediators, including interleukin-6 and vascular endothelial growth factor, as well as alterations in serotonin signaling. These changes may promote tumor growth and metastasis.The authors emphasized that these differences should not be interpreted as mechanisms exclusive to individual cancer types. The available evidence is primarily associative.Therapeutic Approaches Targeting Stress-Related Neuroimmune PathwaysAnother review examined approaches under investigation to modulate neuroimmune pathways activated by chronic stress. These include:1. AnxiolyticsIn an experimental breast cancer model, alprazolam limited tumor progression by acting on a neuroimmune circuit involving glucocorticoids, tumor-associated macrophages, and myeloid-derived suppressor cells.2. Beta-Blockers Such as PropranololThese drugs block beta-adrenergic signaling pathways that contribute to an immunosuppressive environment and tumor progression.In gastric cancer models, propranolol reduced tumor microvascular density and limited metastatic spread.In a pilot study, adding propranolol to chemotherapy in patients with advanced breast cancer was associated with longer progression-free survival.3. Administration of ChemokineIn glioma models, chronic stress promotes tumor progression by reducing the secretion of CCL3 also known as monocyte inflammatory protein-1 alpha, a small, proinflammatory chemokine belonging to the CC chemokine subfamily. Conversely, CCL3 administration has been shown to restore antitumor immunity and enhance the efficacy of anti-PD-1 agents.Psychological Support Is an Important Part of Cancer CareNonpharmacologic psychological interventions aimed at reducing stress-related biological responses may indirectly improve treatment outcomes by strengthening patients’ physiologic resilience.Several approaches have proven effective in reducing psychological distress. Cognitive-behavioral therapies, stress management programs, and mindfulness-based interventions can reduce anxiety and depression and improve quality of life. Studies have reported reductions in cortisol levels and inflammatory markers. Some findings suggest a potential effect on survival, although further research is needed to confirm this association.Although the relationship between chronic stress and cancer progression remains unclear, the authors emphasized the importance of integrating psychological care into the cancer care pathway. Reducing psychological distress appears to be an important goal for improving patients’ quality of life and may also contribute to better clinical outcomes.This story was translated from Univadis France, part of the Medscape Professional Network.