Targeting Strategies for Aberrant Lipid Metabolism Reprogramming and the Immune Microenvironment in Esophageal Cancer: A Review

Table 3

The latest Lipid metabolism drugs with potential clinical use.

Target	Agent	Type	Mechanism	Trial ID or reference
Mitochondrial complex I and metformin ACC	Metformin	ESCC	Metformin can be used as an alternative therapy for chemotherapy- and radiotherapy-refractory esophageal squamous cell carcinoma by inducing cell apoptosis.	[83]
		ESCC	Metformin inhibited the growth and metastasis of ESCC.	[84]
	Metformin with gemcitabine	OSCC	Metformin induces 5-Fu resistance by altering nucleotide metabolism in OSCC.	[85]
	Metformin with cisplatin	ESCC	Metformin combined with chemotherapy can reverse cisplatin resistance by reducing intracellular glutathione levels.	[86]
Natural alkaloid	Berberine	ESCC	By targeting and blocking miR-212, berberine effectively inhibits the invasion and metastasis of ESCC.	[87]
	miR-18b-5p	ESCC	miR-18b-5p regulates de novo lipid synthesis by regulating FASN, ACC1, and SREBP1C and promotes ESCC tumorigenesis and progression.	[33]
Nonsteroidal anti-inflammatory drugs (NSAIDs)	Acetylsalicylic acid (aspirin)	ESCC	Aspirin enhances the therapeutic efficacy of cisplatin in ESCC.	[88]
	Aspirin + statins	OSCC	The combination of aspirin and statin is cost-effective in patients at high risk for progression to esophageal adenocarcinoma.	[89]
HMG-CoA reductase (HMGCR)	Statins (e.g., simvastatin and atorvastatin)	OSCC	The use of statins is associated with a significantly lower incidence of OSCC.	[90]
		ESCC	Atorvastatin inhibits ESCC tumor growth in a PDX model by inhibiting the cAMP and Rap1 signaling pathways.	[91]
Part of carnitine palmitoyltransferase 1 (CPT1)	Carnitine/organic cation transporter novel 2 + Oxaliplatin	ESCC	High expression of OCTN2 promotes the accumulation and cytotoxic activity of oxaliplatin in patients with esophageal cancer, resulting in a reduced risk of recurrence and prolonged survival in EC patients.	[92]
Fatty acid synthase (FASN)	Orlistat (a pancreatic lipase inhibitor developed for obesity treatment), C75, a first-generation synthetic small-molecule inhibitor of FAS, C93, a second-generation small-molecular inhibitor with increased specificity. Previous efforts to treat xenograft cancers with C75	Squamous carcinoma and adenocarcinoma of the esophagus, as well as cases of Barrett’s esophagus with varying levels of dysplasia	FAS is expressed at very high levels in esophageal cancer and growth of these cancers can be inhibited by C93. C75 inhibited OSCC proliferation	[39, 81]
Diferuloylmethane	Curcumin	ESCC/OSCC	Curcumin has influences on FAS activity, FAO, and desaturation system. Curcumin may inhibit the proliferation and colony formation of EC according to dose and time.	[93, 94]
Sterol regulatory element-binding proteins (SREBPs)	Fatostatin (4-hydroxytamoxifen, an active metabolite of tamoxifen)	ESCC	Fatostatin significantly inhibited tumorigenesis by downregulating SREBP1 and EMT markers.	[82]
Estrogen receptor (ER) receptor	Natural estrogen (17b-estradiol) selective ER modulators (SERM) tamoxifen and raloxifene	OSCC and Barrett’s esophagus	Tamoxifen and raloxifene act as agonists of ER signaling, producing pro-apoptotic and growth-inhibitory effects.	[95]
SQLE inhibitor	siRNA	ESCC	The siRNA significantly inhibited the proliferation and invasion of esophageal cancer cells by regulating the expression of cell cycle and EMT-related proteins.	[96, 97]