Fig. 2

Metabolic modulators with anti-CSC effects. Metabolic pathways such those involving glutamine, glycolysis, redox balance, lipids, and autophagy are potentially targetable in CSCs. Some of the metabolic enzymes that are currently being considered as therapeutic targets for CSC are indicated by blue rectangles in the figure. Transcription factor NRF2 plays a pivotal role in both intrinsic resistance and cellular adaptation to ROS and is shown in a yellow rectangle. The carnitine-dependent transporter, which inhibits the mitochondrial import of fatty acids is shown in a yellow ball. Inhibitors are indicated by red rectangles. Abbreviations: ACC, acetyl-CoA carboxylase; Ac-CoA, acetyl-coenzyme A; ACLY, ATP citrate lyase; ACSL, long-chain acyl-CoA synthetases; ATRA, all-trans retinoic acid; 3-BP, 3- bromopyruvate; BSO, L-buthionine-S,R-sulfoximine; CPT1, carnitine palmitoyltransferase; I/Q/II/III/IV/V, complexes of the electron transport chain; DCA, dichloroacetate; 2-DG, 2-deoxy-D-glucose; Doc, doxycycline; FASN, fatty acid synthetase; FAT/CD36, Fatty acid translocase; GCS, gamma glutamyl cysteine synthetase; GLS, glutaminase; GLUT1/4, glucose transporter 1/4; GSH, glutathione; HK2, hexokinase 2; HMG-CoAR, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; 2M14NQ, 2-methylthio-1,4-naphthoquinone; Mito, mitochondrial; NRF2, nuclear factor erythroid 2-related factor 2; OAA, oxaloacetate; PDH, pyruvate dehydrogenase; ROS, reactive oxygen species; TC, tetracyclines; TCA, tricarboxylic acid cycle; SCD1, stearoyl-CoA desaturase-1; SLC1A5, solute carrier family 1 member 5;