The in vivo efficacy of GDC-0152 and LCL161 we observed in this study therefore implied either that the in vivo tumor microenvironment somehow imbued osteosarcoma cells with the ability to produce autocrine TNFα, or that host cells in or around the tumors secreted TNFα that cooperated with the administered Smac mimetics to kill the osteosarcoma cells in vivo. Here, TNF is linked to neoplasm.