MYCN and neuroblastoma: Thus, targeting mTORC1 in combination with ALK leads to enhanced antitumor efficacy and prolongs survival in mouse xenograft models of human NB coexpressing ALKF1174L and MYCN. By contrast, in cells without MYCN amplification, this combination, although inducing downregulation of mTORC1, led to reciprocal upregulation of PI3K activity not only in ALKF1174L-mutated cells but also in those that express the more common ALKR1275Q-mutation.