Chronic Stress As a Modifier of Cancer Biology: Mechanisms Linking Neuroendocrine Signaling to Tumor Initiation, Progression, Metastasis, and Recurrence Publisher

Summary: Can chronic stress influence cancer progression? A review links stress hormones to metabolism, immunity and metastasis; clinical impact remains unclear. #CancerResearch #Stress

Patrad E ; Alizadeh A M
Source: Experimental and Molecular Pathology Published:2026

Abstract

Chronic stress is a systemic disruptor of physiological homeostasis that can influence cancer biology by altering neuroendocrine, immune, metabolic, and stromal processes. While the association between stress and cancer has long been hypothesized, increasing evidence has begun to clarify molecular and cellular mechanisms through which chronic stress may contribute to tumor initiation, progression, and metastasis. This review synthesizes preclinical and clinical evidence indicating that stress-induced dysregulation of catecholamines and glucocorticoids can engage interconnected signaling networks that influence cancer hallmarks in a context-dependent manner. We highlight three interconnected mechanisms, including metabolic adaptation, epigenetic remodeling, and pre-metastatic niche conditioning. Furthermore, we propose a conceptual framework wherein chronic stress may alter apoptotic and anoikis resistance, immune surveillance, extracellular matrix remodeling, and metastatic niche formation across different stages of cancer progression. By integrating evidence across tumor cells, microenvironments, and systemic host responses, we emphasize that the effects of chronic stress are heterogeneous and depend on tumor type, receptor expression, cellular compartment, disease stage, and treatment context. Understanding these interconnected pathways may identify stress-responsive mechanisms of therapeutic relevance, including β-adrenergic and glucocorticoid signaling, while behavioral stress-management interventions may provide complementary approaches. However, whether targeting stress-related pathways can improve cancer outcomes requires validation in well-designed prospective clinical trials. © 2026 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/