The activity of the TWEAK-Fn14 system is enhanced because of the local expression of Fn14 after injury in many tissues, including skeletal muscles, arteries, and liver and in various disease states, such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and cancer leading to activation of MAPKs and canonical and non-canonical NF-κB signaling (Winkles, 2008; Mittal et al, 2010b; Burkly, 2014; Tajrishi et al, 2014; Poveda et al, 2021). This evidence concerns the gene TNFRSF12A and cancer.