Clinical trials have evaluated several markers of target engagement in surrogate tissue such as peripheral blood mononuclear cells (PBMC) or tumor tissue (e.g., degradation of cIAP1 levels due to SMAC mimetics), markers of apoptosis in blood or tumor tissue (e.g., cleavage of caspases or caspase substrates such as PARP or cytokeratin-18), and blood markers of inflammation related to SMAC mimetic-mediated activation of signaling pathways (e.g., increases in inflammatory cytokines such as TNF-α, MCP-1, IL-6, and IL-8)38. Here, TNF is linked to neoplasm.