Table 1.
Selected agents targeting TAMs metabolism.
| Targeted TAMs metabolism | Drug | Targeted Agent | Metabolic modulation | Functions on TAMs | Ref. |
|---|---|---|---|---|---|
| Glucose metabolism | 2-DG | Hexokinase 2 | Aerobic glycolysis inhibition | Macrophage phagocytosis, Repolarization of TAMs | (31, 105, 106) |
| Glucose metabolism | Compound 1 | Lactate dehydrogenase | Decreased lactate production Interfering TME acidity |
Increased M1/M2 ratio in TME | (107) |
| Glucose metabolism | CHC | MCT | sustaining high glycolysis | Repolarization of TAMs | (26) |
| Glucose metabolism; Lipid metabolism | metformin | AMPK mTOR |
increased lipid breakdown, Inhibition of glycolysis | Decreased M2 polarization of macrophages; macrophage infiltration | (25, 81, 82) |
| Glucose metabolism; Lipid metabolism | Olaparib, Niraparib, Talazoparib |
SREBP PARP |
Switch from glycolysis to lipid metabolism, metabolic reprogramming |
modulate macrophage state, phenotype, function, and metabolism. | (108) |
| Glucose metabolism | Shikonin, HA344, |
PKM2 | Inhibition of glycolysis | Suppresses cancer cell proliferation and overcomes, chemotherapeutic drug-mediated resistance | (19, 109, 110) |
| Glucose metabolism; Lipid metabolism | HOE642 | NHE1 | Increases glucose uptake with metabolic shifts towards the OXPHOS metabolism | TAMs polarization and metabolism | (111, 112) |
| Glucose metabolism; Lipid metabolism | DCA AlbA |
PDK | Metabolic shift from glycolysis to OXPHOS | Repolarization of TAMs | (113, 114) |
| Amino acid metabolism | AHRi1, CH-223191 |
AHR | Tryptophan metabolism | Repolarization of TAMs | (39) |
| Amino acid metabolism | JHU083 | GLS1/2 glutamine |
Blocking of glutamine metabolism | Increased M1/M2 ratio in TME, Increased antitumor inflammatory TAMs |
(115, 116) |
| Amino acid metabolism | Methionine Sulfoximine | Glutamine Synthetase | Inhibition of glutamine metabolism, impaired glutamine usage by TAMs | Repolarization of TAMs | (117) |
| Amino acid metabolism | Glufosinate | Glutamine Synthetase |
Inhibition of glutamine metabolism | Repolarization of TAMs | (118) |
| Amino acid metabolism | L-Norvaline, CB-1158 |
Arginase | Inhibition of arginine synthesis, Decreasing arginine levels |
Increased anti-tumoral T cell response in TME, Repolarization of TAMs |
(36) |
| Lipid metabolism | Fatostatin | SREBP | Inhibition of FA metabolism | M2-like TAM polarization | (119) |
| Lipid metabolism | Etomoxir | CPT1 | Impaired lipid oxidation | Decreased M2 activity, TAM infiltration | (120, 121) |
| Lipid metabolism | C75 TVB-2640 |
FASN | Inhibited lipid droplet formation | Increased M1/M2 ratio in TME |
(122) |
| Lipid metabolism | NCX-4016, YVAD, VAD |
Caspase-1/PPARγ | Inhibition of lipid accumulation | TAMs repolarization and differentiation | (123) |
| Lipid metabolism | ATR-101 | ABCA1/ABCG1 | Inhibition of cholesterol efflux | Reprogramming TAMs | (124) |