TNFα, initially named cachectin,16 is probably the most characterized cytokine in cachexia as it promotes anorexia17 and skeletal muscle wasting mainly through the NF-kB pathway.18 TNFα blockade (etanercept) provided promising results in improving cachexia-associated fatigue in a small cohort of cancer patients.19 However, recent trials using neutralizing antibodies against TNFα showed no benefit, suggesting that targeting TNFα alone is not sufficient to prevent cachexia.20 The gene discussed is NFKB1; the disease is cancer.