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.Disclosure of potential conflicts of interest is found at the end of this article.