Here, we provide a molecular basis for this effect, demonstrating that incomplete inhibition of mTORC1 limits the activity of crizotinib in NB cells that express both ALKF1174L and deregulated MYCN. This interpretation is supported by our observation that concomitant inhibition of mTOR restores sensitivity to crizotinib in NB models. This evidence concerns the gene MYCN and neuroblastoma.