Cancer-Induced Fatigue and Cachexia

Cancer-related fatigue (CRF) is a highly prevalent symptom experienced by cancer patients. It is debilitating and has a significant impact on one’s physical, mental and social wellbeing. Currently, the ambiguities surrounding CRF have made the standardization of diagnostic and treatment methods difficult. Although there is limited literature on CRF, several hypotheses have been proposed with regard to its underlying mechanisms. These hypotheses include serotonin dysregulation, hypothalamic pituitary adrenal (HPA) axis dysfunction, afferent nerve activation, the basal ganglia hypothesis and muscle wasting. One of the most promising hypotheses is muscle wasting, involving both the degradation of muscle and the inhibition of muscle regeneration. These pathways are initiated through tumour-induced pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α). Following the activation of nuclear factor kappa-light chain enhancer of activated B-cells (NF-κB), its downstream effects further the progression of muscle wasting. This leads to a more aggravated state known as cachexia. As CRF is multifaceted, further research into the various hypotheses discussed in this chapter would greatly benefit cancer patients experiencing fatigue.