Mechanisms of Cancer-Related Fatigue

Abstract

Cancer-related fatigue (CRF) is one of the most prevalent symptoms patients with cancer experience, both during and after treatment. CRF is pervasive and affects patients' quality of life considerably. It is important, therefore, to understand the underlying pathophysiology of CRF in order to develop useful strategies for prevention and treatment. At present, the etiology of CRF is poorly understood and the relative contributions of the neoplastic disease, various forms of cancer therapy, and comorbid conditions (e.g., anemia, cachexia, sleep disorders, depression) remain unclear. In any individual, the etiology of CRF probably involves the dysregulation of several physiological and biochemical systems. Mechanisms proposed as underlying CRF include 5-HT neurotransmitter dysregulation, vagal afferent activation, alterations in muscle and ATP metabolism, hypothalamic-pituitary-adrenal axis dysfunction, circadian rhythm disruption, and cytokine dysregulation. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is a characteristic, in particular chronic fatigue syndrome and exercise-induced fatigue. The mechanisms that lead to fatigue in these conditions provide a theoretical basis for future research into the complex etiology of this distressing and debilitating symptom. An understanding of relevant mechanisms may offer potential routes for its prevention and treatment in patients with cancer.

Fatigue in hormone-naïve prostate cancer patients treated with radical prostatectomy or definitive radiotherapy

“…36 In this cross-sectional study, without baseline data we can only speculate about the reasons of elevated long-term CF in the RAD group. Except age, the variations in pretreatment demographic and medical variables seemed to have minor effect on this difference.…”

Association between Mitochondrial Bioenergetics and Radiation- Related Fatigue: A Possible Mechanism and Novel Target

“…Although many mechanisms have been proposed for cancer-related fatigue [14][15][16][17][18], the cause remains elusive. Additionally, early biomarkers prognostic for radiation-induced fatigue have not been identified.…”

“…The physiological mechanisms behind fatigue and its increased severity during localized XRT remain unknown. Deficiency of adenosine triphosphate (ATP) has been proposed as the basis of cancer-related fatigue [16,19], but the mechanism has not been explored.…”

Role of physical activity in tumor patients and possible underlying mechanisms

“…Mechanisms proposed as underlying cancer-related fatigue include 5-HT neurotransmitter dysregulation, vagal afferent activation, alterations in muscle and ATP metabolism, hypothalamic-pituitary-adrenal axis dysfunction, circadian rhythm disruption, and cytokine dysregulation. However, to date, the entire etiology of CRF is poorly understood, and the relative contributions of the neoplastic disease, various forms of cancer treatment, and comorbid conditions are widely unknown [67]. Especially, the involvement of oxidative stress as a general mechanism described to induce the fatigue syndrome is rarely evaluated in cancer patients, as well as its correlation to fatigue.…”

“…Animal studies could show that an injection of TNF-α leads to a loss of muscle and fat mass by activating the proteasomal degradation of proteins via the NFκ pathway [67]. Further cachexia-reducing effects have been described for the injection of IFN-γ and IL-6 antibodies [48,90].…”