We, and others, have shown that smac-mimetics function by instigating auto-ubiquitylation and proteasomal degradation of cIAP1 and cIAP2 (284, 285, 288, 289), which in the presence of a stimulus such as TNF, chemotherapy or TLR ligand, results in the formation of a RIPK1/caspase-8 complex, followed by caspase-8 cleavage and the induction of tumor cell death (281, 285, 290, 291). The gene discussed is CASP8; the disease is neoplasm.