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Mechanisms of Cancer-Related Fatigue

^aDepartment of Dermatology, ^bDepartment of Radiation Oncology, ^cDepartment of Family Medicine, ^dDepartment of Environmental Medicine, ^eDepartment of Community and Preventive Medicine, and ^fDepartment of Psychiatry, University of Rochester School of Medicine and Dentistry, James P. Wilmot Cancer Center, Rochester, New York, USA

Key Words. Cancer • Fatigue • Pathophysiology • Etiology

Correspondence: Julie L. Ryan, Ph.D., University of Rochester James P. Wilmot Cancer Center, 601 Elmwood Avenue, Box 704, Rochester, New York 14642, USA. Telephone: 585-275-2282; Fax: 585-461-5601; e-mail: Julie_Ryan{at}urmc.rochester.edu

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.

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