Metabolism, metabolites, and macrophages in cancer

Table 3 Potential druggable targets in reprogramming metabolism

Drug	Target	Effect	Function	Refs.
Depletion of Zeb1	Zeb1	Weakened aerobic glycolysis	Reprogrammed TAM polarization	[150]
SGLT1 inhibitor	SGLT1	Decreased glycolysis	Inhibited M2 polarization	[152]
MIF-CD74 blockade	MIF-CD74	Decreased lactate production	Promoted M1 infiltration	[156]
TLR9 agonist CpG ODN	Wnt2b/β-catenin	Decreased glycolysis	Suppressed M2 polarization	[159]
Rapamycin	mTOR	Remodelled glycolysis metabolism	Reprogrammed M2 to M1	[161]
GARP or integrin inhibitors	GARP/integrin	Upregulated glucose metabolism and OXPHOS gene expression	Restored M1 anti-tumour effect	[163]
Nanoplatform deliver MGLL siRNA and CB-2 siRNA	MGLL/CB-2	Inhibited free fatty acid production	Reprogrammed TAMs to polarize into M1 macrophages	[164]
ABHD5 inhibitor	ABHD5/SRM	Inhibited lipolysis of triglycerides into diglycerides and free fatty acids	Reprogrammed TAM polarization	[165, 166]
PERK inhibitor	PERK	Inhibited glutamine utilization and α-KG concentration	Reduced TAM activity	[167]
Slit2 activator	Slit2	Increased glycolysis, reduced FAO, reduced α-KG-to-succinic acid ratio	Promoted M1 polarization	[168,169]
Nanotherapeutics loaded with TLR7/8 agonist and FAO inhibitor	TLR7/8	Inhibited TCA cycle, upregulated glycolytic metabolic pathway	Reprogrammed M2 to M1	[35]
RIPK3 upregulation	RIPK3	Increased anaerobic glycolysis	Contributed to M1 polarization	[171,172]

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