Extended Data Fig. 4: Effect of proline and arginine amino acid depletion combined with DFMO treatment on MYCN-driven neuroblastoma in vivo.

a) Tumor weight at death in grams for the respective treatment groups. b) Delayed tumor growth as shown by time to palpable tumor onset across all treatment arms. c) Mouse weight at death in grams, adjusted for tumor weight.d) Tumor weight at death in grams, adjusted for mouse weight. e) Kaplan-Meier curve of tumor-free survival in the Th-MYCN model. Treatment groups undergo diet change at day 21 and DFMO treatment via drinking from day 0 and encompass either diet change alone (CD, Pro-free, Arg-free and ProArg-free) or their combination with DFMO. Related to Fig. 2, single amino acid depletion added. f) Tumor growth defined as tumor weight at death normalized by day of life in the single amino acid trial. Mean ± s.e.m. g) Mouse weight under arginine or proline single amino acid free diets compared to combined ProArg-free diets (also in c). h) Tumor weight at sacrifice after late-stage treatment start in the Th-MYCN model (palpable abdominal tumors). Treatment was limited to 14 days after which the mice were sacrificed to obtain tumor weight as primary endpoint. i) Number of mice that were sacrificed before endpoint. In the CD treatment group, four mice died before reaching 14 days, compared to only 1 in ProArg-free-DFMO group. For a, c, d, f g and h: two-tailed t-test compared to CD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. 0.0007. Mean ± s.e.m. For e: Log-rank test p-value compared to CD. For a-g Th-MYCN model, related to Fig. 2: CD n = 13, CD DFMO n = 14, ProArg-free n = 13, ProArg-free DFMO n = 14, Arg-free n = 14, Arg-free n = 15, Pro-free n = 15, Pro-free DFMO n = 15. For h-i Delayed treatment Th-MYCN model: CD n = 11, CD DFMO n = 10, ProArg-free n = 10, ProArg-free DFMO n = 9. Abbreviations: CD treatment, control diet; Pro, proline; Arg, arginine; Free, diet free; DFMO, difluoromethylornithine.

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