Role of growth differentiation factor 15 in cancer cachexia (Review)

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-β family, is a stress-induced cytokine. Under normal circumstances, the expression of GDF15 is low in most tissues. It is highly expressed during tissue injury, inflammation, oxidative stress and cancer. GDF15 has been established as a biomarker in patients with cancer, and is associated with cancer cachexia (CC) and poor survival. CC is a multifactorial metabolic disorder characterized by severe muscle and adipose tissue atrophy, loss of appetite, anemia and bone loss. Cachexia leads to reductions in quality of life and tolerance to anticancer therapy, and results in a poor prognosis in cancer patients. Dysregulated GDF15 levels have been discovered in patients with CC and animal models, where they have been found to be involved in anorexia and weight loss. Although studies have suggested that GDF15 mediates anorexia and weight loss in CC through its neuroreceptor, glial cell-lineage neurotrophic factor family receptor α-like, the effects of GDF15 on CC and the potential regulatory mechanisms require further elucidation. In the present review, the characteristics of GDF15 and its roles and molecular mechanisms in CC are elaborated. The targeting of GDF15 as a potential therapeutic strategy for CC is also discussed.