The Interplay of Chronic Stress and Cancer: Pathophysiology and Implications for Integrated Care

Abstract

Background: Cancer-associated depression is a multifaceted condition that arises from the interplay of biological, psychological, and social factors in individuals diagnosed with cancer. Understanding this condition involves exploring how cancer and its treatments can precipitate depressive symptoms and the mechanisms behind this association. Chronic stress, inflammation, and immunological responses play a crucial role in the development of both cancer and depression. The objective of this review is to describe and synthesize information on the complex interactions between chronic stress, inflammation, immunological responses, and cancer development. Additionally, it aims to review existing evidence regarding mechanisms such as neurotransmitter imbalances, structural brain changes, and genetic predispositions as key contributors to depression in cancer patients.

Recent findings: A comprehensive literature search on Cancer-associated Depression was conducted in electronic databases, including APA PsycINFO, Medline, Google Scholar, Embase, PubMed, Scopus, and Web of Science. The research focused on understanding the potential relationship between stress-induced depression and cancer by examining neurochemical, anatomical, immunological, genetic, and psychological changes. The findings revealed a compilation of both quantitative and qualitative studies on depression in cancer patients. Evidence suggested a potential link between cancer-induced stress and depression, with increased levels of proinflammatory cytokines (such as IL-6) and dysregulation of neurotransmitters, including serotonin, contributing to the onset of depression. Furthermore, studies indicated that antidepressants, along with psychological interventions, were effective in managing depression among cancer patients.

Conclusion: This narrative review provides insights into the importance of integrating oncology and mental health services to address the psychosocial needs of cancer patients. Future research should focus on the bidirectional interactions between stress and cancer, aiming to improve cancer care by incorporating mental health support. Addressing the mental health aspects of cancer treatment can significantly enhance patient outcomes and overall quality of life.

Keywords: cancer; cancer stem cells; chronic stress; counselling; depression; immune modulation; palliative care; psychiatry; psychotherapy; psycho‐oncology.

FIGURE 1

The reciprocal association between cancer and prolonged stress: Hypothalamus‐pituitary–adrenal (HPA) axis is chronically activated in response to chronic stress. Stress hormones can stimulate CSCs by promoting carcinogenesis, supporting the growth and/or progression of cancer, and regulating the microenvironment surrounding tumors through the primary secretion of glucocorticoids (GCs). Moreover, proinflammatory cytokines are produced by both tumors and chronic stress, and these can lead to neuroinflammation and change how the body reacts to stress. Another factor that could lead to a persistent proinflammatory state is anti‐cancer medication [175, 180, 181, 182] (Created in BioRender: https:/biorender.com/h19h122).

FIGURE 2

The essential components required to construct a program for coping with cancer are emphasized (The image has been inspired by Cortiana et al. [28]) (Created in BioRender: https:/biorender.com/h19h122).