Table 1.

Mechanisms of chemoresistance type 1 (MOC-1) and 2 (MOC-2) to drugs clinically used in HCC (hepatocellular carcinoma).

Protein	Change	Drugs Affected	Consequences	Reference
Uptake Carriers (MOC-1a)
OCT1	Down-regulation	Sorafenib	Reduced OS	[11]
OCT1	Mutations		Decreased function in vitro	[9]
SLC46A3	Down-regulation		Reduced OS	[18]
Export Pumps (MOC-1b)
BCRP	Up-regulation	Sorafenib	Reduced OS	[19]
MDR1	Up-regulation		Reduced MST	[20]
MDR1	GV: rs1045642		Better clinical evolution	[21]
MRP3	Up-regulation		Decreased cell sensitivity in vitro	[22]
Drug Metabolism (MOC-2)
CYP3A4	GV: rs2242480	Lenvatinib	Altered plasma levels	[23]
CYP3A5	GV: rs776746	Sorafenib	Hepatic and renal toxicity	[24]
DPD	Up-regulation	5-Fluorouracil	Higher DPR and lower PFS	[25]
DPD	Up-regulation	S-1	Increased OS	[26]
DPD	Up-regulation	Interferon-α	Reduced OS	[27]
UGT1A1	GV: rs8175347	Sorafenib	Hyperbilirubinemia and toxicity	[28]
UGT1A9	Down-regulation		Reduced OS	[29]
UGT1A9	GV: rs3832043		Severe toxicity	[30]
UGT1A9	GV: rs17868320		Severe toxicity	[31]
UGT1A9	GV: rs3832043	Regorafenib	Severe toxicity	[32]

DPR, disease progression rate; GV, genetic variant; MST, median survival time; OS, overall survival; PFS, progression-free survival.