The Role of Psychologic Stress in Cancer Initiation: Clinical Relevance and Potential Molecular Mechanisms

Falcinelli, Marta; Thaker, Premal H.; Lutgendorf, Susan K.; Conzen, Suzanne D.; Flaherty, Renée L.; Flint, Melanie S.

doi:10.1158/0008-5472.can-21-0684

Cited by 28 publications

(30 citation statements)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chronic stress stimulates corticotropin-releasing hormone (CRH) release from the hypothalamus and adrenocorticotropic hormone (ACTH) secretion from the pituitary gland, then ACTH triggers the adrenal gland cortex to release cortisol into blood. Catecholamine (epinephrine, norepinephrine and dopamine) is produced from both the adrenal gland medulla and nerve fiber endings ( 4 , 8 , 44 ). All of these stress-related hormones play biological roles through binding to corresponding receptors distributed on the surface of diverse types of cells ( Figure 1 ).…”

Section: The Interaction Of Stress Neuroendocrine and Immunity In Cancermentioning

confidence: 99%

See 1 more Smart Citation

Stress and cancer: The mechanisms of immune dysregulation and management

et al. 2022

View full text Add to dashboard Cite

Advances in the understanding of psychoneuroimmunology in the past decade have emphasized the notion that stress and cancer are interlinked closely. Durable chronic stress accelerated tumorigenesis and progression, which is unfavorable for clinical outcomes of cancer patients. Available evidence has provided unprecedented knowledge about the role and mechanisms of chronic stress in carcinogenesis, the most well-known one is dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). With abnormal activation of neuroendocrine system, stress-related hormones contribute to increased oncogenes expression, exacerbated chronic inflammation and impaired immunologic function. In addition, accumulating studies have demonstrated that diverse stress interventions including pharmacological approaches, physical exercises and psychological relaxation have been administered to assist in mental disorders reduction and life quality improvement in cancer patients. In this review, we systematically summarize the connection and mechanisms in the stress-immune-cancer axis identified by animal and clinical studies, as well as conclude the effectiveness and deficiencies of existing stress management strategies.

show abstract

Section: The Interaction Of Stress Neuroendocrine and Immunity In Cancermentioning

confidence: 99%

“…Chronic exposure to stressors promotes tumorigenesis and development. Meanwhile, some psychosomatic symptoms such as anxiety, fatigue, or depression during survivorship can also act as the sources of stress to exacerbate tumor progression (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Stress and cancer: The mechanisms of immune dysregulation and management

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Although the clinical evidence of the association between psychological distress and tumorigenesis is still controversial ( 34 ), some preclinical studies have suggested the possibility of distress involved in tumorigenesis. DNA damage can cause somatic mutations and genomic instability, which may promote tumorigenesis ( 35 ).…”

Section: Psychological Distress and Cancermentioning

confidence: 99%

Psychological distress and eustress in cancer and cancer treatment: Advances and perspectives

Zhou

Zhang

et al. 2022

Sci. Adv.

View full text Add to dashboard Cite

Facing cancer diagnosis, patients with cancer are prone to psychological stress and consequent psychological disorders. The association between psychological stress and cancer has long been a subject of high interest. To date, preclinical studies have gradually uncovered the promotive effects of psychological distress on tumor hallmarks. In contrast, eustress may exert suppressive effects on tumorigenesis and beneficial effects on tumor treatment, which brings a practicable means and psychosocial perspective to cancer treatment. However, the underlying mechanisms remain incompletely understood. Here, by focusing on the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, as well as stress-related crucial neurotransmitters and hormones, we highlight the effects of distress and eustress on tumorigenesis, the tumor microenvironment, and tumor treatment. We also discuss the findings of clinical studies on stress management in patients with cancer. Last, we summarize questions that remain to be addressed and provide suggestions for future research directions.

show abstract

“…It has been postulated that this could be due to dysfunction of the receptor/Gs/AC complex. To date, it remains unclear which abnormalities in peripheral cells are identified with the pathophysiology of mood disorders and are associated with nonspecific stress or homeostatic mechanisms through both alpha2 and beta2 observations [43][44][45].…”

Section: Studies On Peripheral Blood Cellsmentioning

confidence: 99%

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Rahman

Islam

Mim

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

G protein-coupled receptors (GPCRs) are intricately involved in the conversion of extracellular feedback to intracellular responses. These specialized receptors possess a crucial role in neurological and psychiatric disorders. Most nonsensory GPCRs are active in almost 90% of complex brain functions. At the time of receptor phosphorylation, a GPCR pathway is essentially activated through a G protein signaling mechanism via a G protein-coupled receptor kinase (GRK). Dopamine, an important neurotransmitter, is primarily involved in the pathophysiology of several CNS disorders; for instance, bipolar disorder, schizophrenia, Parkinson’s disease, and ADHD. Since dopamine, acetylcholine, and glutamate are potent neuropharmacological targets, dopamine itself has potential therapeutic effects in several CNS disorders. GPCRs essentially regulate brain functions by modulating downstream signaling pathways. GPR6, GPR52, and GPR8 are termed orphan GPCRs because they colocalize with dopamine D1 and D2 receptors in neurons of the basal ganglia, either alone or with both receptors. Among the orphan GPCRs, the GPR52 is recognized for being an effective psychiatric receptor. Various antipsychotics like aripiprazole and quetiapine mainly target GPCRs to exert their actions. One of the most important parts of signal transduction is the regulation of G protein signaling (RGS). These substances inhibit the activation of the G protein that initiates GPCR signaling. Developing a combination of RGS inhibitors with GPCR agonists may prove to have promising therapeutic potential. Indeed, several recent studies have suggested that GPCRs represent potentially valuable therapeutic targets for various psychiatric disorders. Molecular biology and genetically modified animal model studies recommend that these enriched GPCRs may also act as potential therapeutic psychoreceptors. Neurotransmitter and neuropeptide GPCR malfunction in the frontal cortex and limbic-related regions, including the hippocampus, hypothalamus, and brainstem, is likely responsible for the complex clinical picture that includes cognitive, perceptual, emotional, and motor symptoms. G protein and GPCR-mediated signaling play a critical role in developing new treatment options for mental health issues, and this study is aimed at offering a thorough picture of that involvement. For patients who are resistant to current therapies, the development of new drugs that target GPCR signaling cascades remains an interesting possibility. These discoveries might serve as a fresh foundation for the creation of creative methods for pharmacologically useful modulation of GPCR function.

show abstract

The Role of Psychologic Stress in Cancer Initiation: Clinical Relevance and Potential Molecular Mechanisms

Cited by 28 publications

References 141 publications

Stress and cancer: The mechanisms of immune dysregulation and management

Stress and cancer: The mechanisms of immune dysregulation and management

Psychological distress and eustress in cancer and cancer treatment: Advances and perspectives

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Contact Info

Product

Resources

About