The article discusses how tryptophan (Trp) fuels MYC-dependent liver tumorigenesis through the synthesis of indole 3-pyruvate (I3P). Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells, and understanding these differences can reveal vulnerabilities for targeted cancer therapies. The study shows that MYC-driven liver tumors rely on increased Trp uptake, but Trp utilization in the kynurenine (Kyn) pathway is reduced. Depriving these tumors of Trp through a No-Trp diet prevents tumor growth and restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unaffected in liver cancer cells. The study identifies I3P as a crucial metabolite for liver tumor growth, and I3P supplementation restores the growth of Trp-starved liver cancer cells. These findings suggest that targeting I3P could be a potential therapeutic strategy for MYC-driven cancers. The research also highlights the importance of characterizing nutrient demands of different tumor types to identify specific vulnerabilities for targeted interventions. The study further explores the role of Trp and its metabolites in liver cancer, showing that while Kyn levels are increased in some cancers, I3P is the key metabolite that supports tumor growth. The results demonstrate that Trp starvation can rescue normal liver expression profiles in MYC-ON tumors and that I3P plays a critical role in tumor growth. The study concludes that understanding the nutritional needs of liver cancer cells can open new avenues for therapeutic interventions.The article discusses how tryptophan (Trp) fuels MYC-dependent liver tumorigenesis through the synthesis of indole 3-pyruvate (I3P). Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells, and understanding these differences can reveal vulnerabilities for targeted cancer therapies. The study shows that MYC-driven liver tumors rely on increased Trp uptake, but Trp utilization in the kynurenine (Kyn) pathway is reduced. Depriving these tumors of Trp through a No-Trp diet prevents tumor growth and restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unaffected in liver cancer cells. The study identifies I3P as a crucial metabolite for liver tumor growth, and I3P supplementation restores the growth of Trp-starved liver cancer cells. These findings suggest that targeting I3P could be a potential therapeutic strategy for MYC-driven cancers. The research also highlights the importance of characterizing nutrient demands of different tumor types to identify specific vulnerabilities for targeted interventions. The study further explores the role of Trp and its metabolites in liver cancer, showing that while Kyn levels are increased in some cancers, I3P is the key metabolite that supports tumor growth. The results demonstrate that Trp starvation can rescue normal liver expression profiles in MYC-ON tumors and that I3P plays a critical role in tumor growth. The study concludes that understanding the nutritional needs of liver cancer cells can open new avenues for therapeutic interventions.