Recently, the second generation of TRAIL agonists, such as rsTRAIL fused to Fc, single chain of monoclonal antibodies targeting DR4/DR5 functionalized to nanoparticles or linkers, in order to increase their agonistic activity and efficacy for cancer therapy, have been developed in the preclinical or early clinical trials 8, 18, 19, indicating that the second generation of TRAIL receptor agonists or their derivatives may raise up a new hope for TRAIL receptor targeting cancer therapy. Here, TNFRSF10B is linked to cancer.