Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma

Table 3 Identified drugs and their targets for drug repurposing in hepatocellular carcinoma

Drug	Original therapeutic indication	Molecular targets in HCC	Ref.
Antihistamines	Allergy	H1R-H4R, Eag1, CYP2J2, TRPV2, AP-1, NF-B	[88,91,96,98,102,103,105,109,111,113,115,116]
Raloxifene, bazedoxifene	Breast cancer (raloxifene), osteoporosis	ER-, ER-, GPER, IL-6R, aHR, NF-B, STAT3, PI3K/AKT, MAPK	[135-137,141,142]
Disulfiram	Alcoholism	NF-B, TGF-β, ROS-JNK	[149-151,157]
Clofazimine	Antimycobacterial used to treat leprosy	Wnt/-catenin pathway	[166-178]
Albendazole	Anthelmintic	Tubulin, ERK1/2-HIF-1α-p300/CREB	[175]
Pimozide	Antipsychotic used to manage Tourette's Disorder	STAT3, Wnt/-catenin	[185,188]
Natamycin	Macrolide antifungal	PRDX1	[191]
Metformin	Glycemic control in type 2 diabetes mellitus	PI3K-mTOR pathway, AMPK	[200-202,206,207]
Valproate	Anticonvulsant	HDAC, Notch-1, MAPK pathway, -catenin pathway	[220,221,223]
Atorvastatin	Lower lipid levels and reduce the risk of cardiovascular disease	Mevalonate pathway	[231]
Celebrex	NSAID	COX-2, PNO1	[237,243]
Hydroxychloroquine	Antimalarial	Autophagy inhibition, TLR9 pathway	[247]

NSAID: Non-steroidal anti-inflammatory drug; mTOR: Mechanistic target of rapamycin; HCC: Hepatocellular carcinoma; NF-kB: Nuclear factor kB; AP-1: Activating protein-1; CYP2J2: Cytochrome P450 2J2; ER: Oestrogen receptor; IL-6R: Interleukin-6R; STAT3: Signal transducer and activator of transcription 3; PI3K: Phosphoinositide 3-kinase; TGF-β: Transforming growth factor-β; PRDX1: Peroxiredoxin 1; HDAC: Histone deacetylase; aHR: Adjusted hazard ratio.