Figure 1.

Schematic diagram illustrating the metabolic alterations underlying the shifts between differentiated versus cancer stem cell states; epithelial and mesenchymal states; and treatment-sensitive or resistant states. Crucial interactions with the tumor microenvironment that are key determinants of metabolic rewiring within the cancer cells are also depicted. Upregulated metabolites and processes are indicated in black. Downregulated metabolic processes are indicated with a black downward-pointing arrow. Processes for which evidence remains confounding are italicized. Metabolic drugs capable of causing a shift in cell states are indicated in red. ECM, extracellular matrix; CAFs, cancer-associated fibroblasts; Asn, asparagine; Gln, glutamine; AA, amino acid; OxPhos, oxidative phosphorylation; ROS, reactive oxygen species; Met, methionine; 2HG, 2-hydroxyglutarate; FA, fatty acid; FAO, fatty acid oxidation.