In this study, we investigate the effect of IAPs inhibition by recently developed SMAC-mimetics Birinapant and AT-406 in colorectal tumour cells, their cross-talk with the TRAIL-induced apoptotic pathway, BRAF and BCL-2 oncogenic pathways and the underlying mechanisms that can efficiently overcome tumour resistance to apoptosis. The gene discussed is TNFSF10; the disease is colorectal neoplasm.