The observation that osteosarcoma cells were sensitive in vitro to TNFα combined with physiologically achievable concentrations of Smac mimetics, coupled with these suggestions that osteosarcomas may contain high levels of TNFα, prompted us to examine the anti-osteosarcoma activity of selected Smac mimetics in vivo, as sole agents or in combination with doxorubicin, using nude mice implanted subcutaneously or intramuscularly with murine or human osteosarcoma cells. This evidence concerns the gene TNF and osteosarcoma.