In this study, to define its mechanism of action via other cell-death pathways in addition to apoptosis, we showed that ZOL induced autophagy in OS cell lines (as in vivo orthotopic tumor models) and in OS patient-derived cells (through the Akt/mTOR/p70S6K and Erk signaling pathways), and that autophagy suppression may attenuate the anticancer effect of ZOL. This evidence concerns the gene MTOR and neoplasm.