biostudies-literatureFroldi FCancer Research UKFrancis Crick InstituteMedical Research CouncilThe Francis Crick InstituteNational Health and Medical Research CouncilWellcome Truste99895https://www.ebi.ac.uk/biostudies/studies/S-EPMC6443203biostudies-literatureUnknown38(7)Rewired metabolism of glutamine in cancer has been well documented, but less is known about other amino acids such as histidine. Here, we use <i>Drosophila</i> cancer models to show that decreasing the concentration of histidine in the diet strongly inhibits the growth of mutant clones induced by loss of Nerfin-1 or gain of Notch activity. In contrast, changes in dietary histidine have much less effect on the growth of wildtype neural stem cells and <i>Prospero</i> neural tumours. The reliance of tumours on dietary histidine and also on histidine decarboxylase (Hdc) depends upon their growth requirement for Myc. We demonstrate that Myc overexpression in <i>nerfin-1</i> tumours is sufficient to switch their mode of growth from histidine/Hdc sensitive to resistant. This study suggests that pThe EMBO journalHistidine is selectively required for the growth of Myc-dependent dedifferentiation tumours in the &lt;i&gt;Drosophila&lt;/i&gt; CNS.PMC6443203MC_U11758423710029104566/Z/14/ZMC_U11753388710088FC001088APP1044704Gould APFroldi FPachnis PCheng LYSzuperak MFernando TCostas OfalseHistidine is selectively required for the growth of Myc-dependent dedifferentiation tumours in the &lt;i&gt;Drosophila&lt;/i&gt; CNS.Rewired metabolism of glutamine in cancer has been well documented, but less is known about other amino acids such as histidine. Here, we use <i>Drosophila</i> cancer models to show that decreasing the concentration of histidine in the diet strongly inhibits the growth of mutant clones induced by loss of Nerfin-1 or gain of Notch activity. In contrast, changes in dietary histidine have much less effect on the growth of wildtype neural stem cells and <i>Prospero</i> neural tumours. The reliance of tumours on dietary histidine and also on histidine decarboxylase (Hdc) depends upon their growth requirement for Myc. We demonstrate that Myc overexpression in <i>nerfin-1</i> tumours is sufficient to switch their mode of growth from histidine/Hdc sensitive to resistant. This study suggests that p2019-01-01T00:00:00Z2019 Apr2026-07-17T01:31:31.53Z2019-06-06T21:04:46ZS-EPMC64432033080400410.15252/embj.201899895