GFRAL and obesity due to melanocortin 4 receptor deficiency: Indeed, obesity is an important predisposing factor for cancer, including digestive system malignancies 54, and GDF15 is an etiological agent in cancer-related anorexia/cachexia syndrome (CACS) 55, as up-regulated GDF15 serum level was found to be a factor reducing appetite and body weight 19, and inhibition of GDF15-GFRAL activity prevents cancer cachexia 56.