Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies

Abstract

Anorexia and reduced food intake are important issues in the management of patients with cancer because they contribute to the development of malnutrition, increase morbidity and mortality, and impinge on quality of life. Accumulating evidence indicates that cancer anorexia is multifactorial in its pathogenesis, and most of the hypothalamic neuronal signalling pathways modulating energy intake are likely to be involved. Several factors are considered to be putative mediators of cancer anorexia, including hormones (eg, leptin), neuropeptides (eg, neuropeptide Y), cytokines (eg, interleukin 1 and 6, and tumour necrosis factor), and neurotransmitters (eg, serotonin and dopamine). These pathways are not isolated and distinct pathogenic mechanisms but are closely inter-related. However, convincing evidence suggests that cytokines have a vital role, triggering the complex neurochemical cascade which leads to the onset of cancer anorexia. Increased expression of cytokines during tumour growth prevents the hypothalamus from responding appropriately to peripheral signals, by persistently activating anorexigenic systems and inhibiting prophagic pathways. Hypothalamic monoaminergic neurotransmission may contribute to these effects. Thus, the optimum therapeutic approach to anorectic cancer patients should include changes in dietary habits, achieved via nutritional counselling, and drug therapy, aimed at interfering with cytokine expression or hypothalamic monoaminergic neurotransmission.