MYCN-amplified NB cells with activating transcription factor 4 (ATF4) expression showed increased transcriptional activation of this metabolic pathway and small molecules targeting SGOC-induced metabolic stress and autophagy in cell lines and xenograft models.94 Moreover, MYCN was shown to directly activate the expression of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), an important enzyme in the folate cycle, maintaining NADPH redox homeostasis in MYCN-amplified NB. This evidence concerns the gene MTHFD1 and neuroblastoma.