The article discusses the reprogramming of cellular metabolism in cancer, challenging the traditional view that altered metabolism is a passive response to damaged mitochondria. It highlights recent evidence that metabolites can themselves be oncogenic by altering cell signaling and blocking differentiation. The authors argue that altered metabolism is a core hallmark of cancer, driven by oncogenes and tumor suppressors. They explore how mitochondrial metabolism is reprogrammed to support anabolic growth, and how this reprogramming can influence cellular differentiation. The article also delves into the role of specific metabolic enzymes, such as pyruvate kinase M2 (PKM2), and the discovery of oncometabolites like 2-hydroxyglutarate (2HG). Finally, it addresses the challenges in studying cancer metabolism, including the inability to reliably distinguish metabolites from different compartments and the non-cell autonomous effects of tumor metabolism.The article discusses the reprogramming of cellular metabolism in cancer, challenging the traditional view that altered metabolism is a passive response to damaged mitochondria. It highlights recent evidence that metabolites can themselves be oncogenic by altering cell signaling and blocking differentiation. The authors argue that altered metabolism is a core hallmark of cancer, driven by oncogenes and tumor suppressors. They explore how mitochondrial metabolism is reprogrammed to support anabolic growth, and how this reprogramming can influence cellular differentiation. The article also delves into the role of specific metabolic enzymes, such as pyruvate kinase M2 (PKM2), and the discovery of oncometabolites like 2-hydroxyglutarate (2HG). Finally, it addresses the challenges in studying cancer metabolism, including the inability to reliably distinguish metabolites from different compartments and the non-cell autonomous effects of tumor metabolism.