Chronic stress: a fourth etiology in tumorigenesis?

Abstract Chronic stress, driven by persistent psychological, environmental, or physiological factors, is a prolonged heightened state of stress response that disrupts homeostasis. When unmanaged, it will lead to sustained negative emotions such as depression, loneliness, anxiety, and emotional adver...

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Main Authors: Asra khan, Mengqiu Song, Zigang Dong
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Molecular Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12943-025-02402-x
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author Asra khan
Mengqiu Song
Zigang Dong
author_facet Asra khan
Mengqiu Song
Zigang Dong
author_sort Asra khan
collection DOAJ
description Abstract Chronic stress, driven by persistent psychological, environmental, or physiological factors, is a prolonged heightened state of stress response that disrupts homeostasis. When unmanaged, it will lead to sustained negative emotions such as depression, loneliness, anxiety, and emotional adversity. This persistent emotional distress not only exacerbates mental health disorders but also poses significant risks to physical health. Increasing evidence suggests a strong link between chronic stress, stress-related hormones, and the rising incidence of malignancies. As a result, chronic stress might be recognized as a potential “fourth etiology” of cancer, alongside physical, chemical, and biological carcinogens. As a potential etiological driver of tumorigenesis, chronic stress-related hormones such as glucocorticoids and catecholamines or neurotransmitters have been implicated in various aspects of tumor initiation, promotion, and progression. Additionally, chronic stress influences tumorigenesis through multiple mechanisms, including tumor microenvironment remodeling, microbial dysbiosis, drug resistance promotion, as well as the regulation of oncogenic signaling pathways. Hence, mitigating the impact of chronic stress could be an effective method of cancer prevention and therapy. However, it remains a significant challenge in the assessment of chronic stress as a cancer etiology. Moreover, the link between stress-associated obesity and cancer offers novel insights into underlying mechanistic pathways in cancer research. Repurposing preventive and therapeutic approaches targeting stress-related tumorigenesis may provide deeper insights into the interplay between chronic stress and cancer, ultimately improving patient outcomes and quality of life.
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spelling doaj-art-f3cb091dc6884fd8bf20f3919368f4612025-08-20T03:42:20ZengBMCMolecular Cancer1476-45982025-07-0124112210.1186/s12943-025-02402-xChronic stress: a fourth etiology in tumorigenesis?Asra khan0Mengqiu Song1Zigang Dong2Department of Pathophysiology, School of Basic Medical Sciences, Henan Medical College, Zhengzhou UniversityDepartment of Pathophysiology, School of Basic Medical Sciences, Henan Medical College, Zhengzhou UniversityDepartment of Pathophysiology, School of Basic Medical Sciences, Henan Medical College, Zhengzhou UniversityAbstract Chronic stress, driven by persistent psychological, environmental, or physiological factors, is a prolonged heightened state of stress response that disrupts homeostasis. When unmanaged, it will lead to sustained negative emotions such as depression, loneliness, anxiety, and emotional adversity. This persistent emotional distress not only exacerbates mental health disorders but also poses significant risks to physical health. Increasing evidence suggests a strong link between chronic stress, stress-related hormones, and the rising incidence of malignancies. As a result, chronic stress might be recognized as a potential “fourth etiology” of cancer, alongside physical, chemical, and biological carcinogens. As a potential etiological driver of tumorigenesis, chronic stress-related hormones such as glucocorticoids and catecholamines or neurotransmitters have been implicated in various aspects of tumor initiation, promotion, and progression. Additionally, chronic stress influences tumorigenesis through multiple mechanisms, including tumor microenvironment remodeling, microbial dysbiosis, drug resistance promotion, as well as the regulation of oncogenic signaling pathways. Hence, mitigating the impact of chronic stress could be an effective method of cancer prevention and therapy. However, it remains a significant challenge in the assessment of chronic stress as a cancer etiology. Moreover, the link between stress-associated obesity and cancer offers novel insights into underlying mechanistic pathways in cancer research. Repurposing preventive and therapeutic approaches targeting stress-related tumorigenesis may provide deeper insights into the interplay between chronic stress and cancer, ultimately improving patient outcomes and quality of life.https://doi.org/10.1186/s12943-025-02402-xChronic stressHPA axis and SNSStress hormonesTumorigenesis
spellingShingle Asra khan
Mengqiu Song
Zigang Dong
Chronic stress: a fourth etiology in tumorigenesis?
Molecular Cancer
Chronic stress
HPA axis and SNS
Stress hormones
Tumorigenesis
title Chronic stress: a fourth etiology in tumorigenesis?
title_full Chronic stress: a fourth etiology in tumorigenesis?
title_fullStr Chronic stress: a fourth etiology in tumorigenesis?
title_full_unstemmed Chronic stress: a fourth etiology in tumorigenesis?
title_short Chronic stress: a fourth etiology in tumorigenesis?
title_sort chronic stress a fourth etiology in tumorigenesis
topic Chronic stress
HPA axis and SNS
Stress hormones
Tumorigenesis
url https://doi.org/10.1186/s12943-025-02402-x
work_keys_str_mv AT asrakhan chronicstressafourthetiologyintumorigenesis
AT mengqiusong chronicstressafourthetiologyintumorigenesis
AT zigangdong chronicstressafourthetiologyintumorigenesis