Sestrin Family of Genes and their Role in Cancer-related Fatigue

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Cancer-related fatigue (CRF) continues to be a prevalent and distressing symptom experienced by cancer patients and survivors. CRF is defined by the National Comprehensive Cancer Network as a “distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning [1].” Although there is currently no optimal management and scant molecular evidence to guide the development of effective CRF therapies, several pathophysiological mechanisms have been proposed to explain the development of CRF [2, 3]. These pathophysiological mechanisms of CRF are believed to be complex and involve a cascade of events including the dysregulation of several physiological and biochemical systems, such as oxidative stress, inflammation, immune modulation, circadian rhythms modulation, growth factors, serotonin dysregulation, hypothalamic-pituitary-adrenal-axis disruption, vagal afferent activation, and hematopoietic dysfunction [2,3,4]. Although these proposed mechanisms of CRF pathophysiology are yet to be independently investigated, recent evidence suggest a critical role of mitochondrial dysfunction/oxidative stress in CRF [4, 5].

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Supportive Care in Cancer, v. 26, p. 2071-2074