Lipid metabolism reprogramming in tumor-associated macrophages and implications for therapy

Table 1 Drugstargeting lipid metabolism in TAMs

Drug	Target	Metabolic pathway/consequence	Clinical trials	Phase	Disease model
Enhance immunotherapy effect
Fatostatin [70]	SREBP1	Inhibit de novo synthesis of fatty acids in TAMs			Melanoma
Etomoxir [72]	CPT-1A	Inhibit FAO-dependent ROS and NOD-like receptor thermoprotein			Liver Cancer
RQ treatment [73]	Cellular autophagy	Increase ratio of M1/M2 TAMs and CD8/CD4 + T cells			Glioblastoma
IP549 [15]	PI3K-γ	Reduce lipids in TAMs			Gastric Cancer
Decitabine [27]	Inhibit FAO	Inhibit pro-tumor polarization of TAMs			Liver Cancer
Improve chemotherapy resistance
SB431542 [16]	SMAD signaling pathway	Inhibit SMAD-GDF15-FAO			Colorectal Cancer
GB111-NH2 [74]	Histone	Inhibit histones B, L and S
C75 [10]	FASN	Enhance cisplatin-induced apoptosis in tumor cells			TNBC
Simvastatin [75]	HMG-CoA reductase	Inhibit integrin/FAK/ERK signaling pathway and EMT	NCT00452244 NCT00452634 NCT01441349 NCT04985201 NCT04698941 NCT01156545 NCT02197234	Phase 2 Phase 2 Phase 2 Phase 2 Phase 2 Phase 2 Phase 1	Lung Cancer
Lovastatin [76]	HMG-CoA reductase	Downregulate IL-10 and upregulate IFN-γ	NCT00285857 NCT00902668 NCT00584012	Phase 2 Phase 2 Phase 2	Breast Cancer
Other drugs
Zileuton [49, 50]	5-LOX	Reduce MMP-7 and inhibit TAMs migration and infiltration	NCT00056004 NCT00070486	Phase 2 Phase 2	Ovarian Cancer Lung Cancer
NCX-4016 [23]	Caspase-1	Induce apoptosis and inhibit the growth of tumor cells	NCT00331786	Phase 1	Colon Cancer
ATR101 [59]	ABC	Inhibit cholesterol efflux from TAMs			Lung Cancer

ISSN: 1476-511X