Advances in Targeted Drug Resistance Associated with Dysregulation of Lipid Metabolism in Hepatocellular Carcinoma

Figures & data

Figure 1 Deregulated alterations of fatty acid and cholesterol metabolism in hepatocellular carcinoma. The glycolysis pathway: GLUTs, glucose transporters; PDH, pyruvate dehydrogenase. Cholesterol metabolism: HMG-CoA, 3-hydroxy-3-methylglutaryl coenzymeA; LDL, low density lipoprotein.

Abbreviations: HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A reductase; The synthesis and uptake of fatty acids: FABPs, fatty acid binding protein; CD36, fatty acid translocase; ACLY, ATPcitrate lyase; ACC, acetyl-CoA carboxylase; FASN, fatty acid synthase; FAs, fatty acids; SCD1, Stearoyl-CoA desaturase 1; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acids; TAG, triacylglycerol; DAG, diacylglycerol; ACS, Acyl-CoA Synthetase. Fatty acid β-oxidation: CPT1, carnitine palmitoyltransferase 1; CPT2, carnitine palmitoyltransferase 2; ACOX1, acyl-coenzyme A oxidase 1. HCC, hepatocellular carcinoma.

Table 1 The Impact of Therapeutic Drugs Targeting the Lipid Metabolism Pathway on the Treatment of Hepatocellular Carcinoma

Type of Lipid Metabolism	Drugs	The main mechanism of drugs	Reference
Fatty acid	Orlistat	Improving Sorafenib resistance by inhibiting the expression of FASN	[71]
	TVB-2640	Enhancing the sensitivity of Sorafenib treatment by inhibiting the expression of FASN	[72]
	TVB3664	Enhancing the therapeutic efficacy of Cabozantinib and Sorafenib by Inhibiting the expression of FASN	[73]
	SSI-4	Enhancing the therapeutic efficacy of Sorafenib by Inhibiting the expression of SCD1	[45]
	SSO	Inhibition of the uptake of fatty acids and oxLDL mediated by CD36 through competitively binding with CD36	[77]
	VT1021	Specifically targeting CD36 to inhibit fatty acid uptake	[78]
	SB-204990	Suppressing the proliferation of hepatocellular carcinoma cells by Inhibiting the expression of ACLY	[80]
	ECT-1002	Suppressing the proliferation of hepatocellular carcinoma cells by Inhibiting the expression of ACLY	[81]
	BMS-303141	Enhancing the therapeutic efficacy of Sorafenib by Inhibiting the expression of ACLY	[82]
Cholesterol	Simvastatin	Enhancing the efficacy of Sorafenib by inhibiting cholesterol synthesis through Inhibiting the activity of HMGCR	[83]
	Maprotiline	Enhancing the efficacy of Sorafenib by inhibiting cholesterol synthesis through the reduction of SREBP2 phosphorylation.	[49]

Abbreviations: FASN, fatty acid synthase; SCD1, stearoyl-CoA desaturase 1; ACLY, ATPcitrate-lyase; CD36, fatty acid translocase; oxLDL, oxidized low-density lipoprotein; SSO, Sulfo-N-succinimidyl oleate; HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A reductase; SREBP2, Sterol Regulatory Element-Binding Protein 2.

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