Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma

Table 1 Human ABC transporter genes and proteins conferred drug resistance

Official symbol	Alternative name	Members	Proteins associated with drug resistance	Resistant drugs
ABCA		13 (ABCA1 to ABCA13)	ABCA2	Mitoxantrone
ABCB	MDR	11 (ABCB1 to ABCB11)	ABCB1 (MDR1/PGP)	Doxorubicin, colchicine, etoposide, paclitaxel, cisplatin, methotrexate, daunorubicin, camptothecin
			ABCB11 (BSEP)	5-fluorouracil, paclitaxel
ABCC	MRP	13 (ABCC1 to ABCC13)	ABCC1 (MRP1)	Doxorubicin, daunorubicin, methotrexate, colchicine
			ABCC2 (MRP2)	Doxorubicin, cisplatin, etoposide
			ABCC3 (MRP3)	Methotrexate, etoposide
			ABCC6 (MRP6)	Etoposide
			ABCC10 (MRP7)	Vinorelbine, paclitaxel, docetaxel
			ABCC11 (MRP8)	5-fluorouracil, tamoxifen, paclitaxel
ABCD	ALD	4 (ABCD1 to ABCD4)
ABCE	OABP	1 (ABCE1)
ABCF	GCN20	3 (ABCF1 to ABCF3)
ABCG	White	5 (ABCG1, ABCG2, ABCG4, ABCG5, ABCG8)	ABCG2 (BCRP)	Mitoxantrone, topotecan, doxorubicin, daunorubicin, cisplatin, etoposide

Table 2 Several potential inhibitors and targeted agents of growth factor receptors, signaling pathways and ABC transporters in liver cancer

Targets		Agents	Ref.
ABC transporters	ABCB1/MDR1	Verapamil, cyclosporine, GF120918, PSC833, GG918, biricodar	[146-149]
	ABCC1/MRP1	Cyclosporine, biricodar	[146,149]
	ABCG2/BCRP	FTC, Kol43, GF120918, novobiocin, naringenin	[69,70,147,150,151]
Growth factor receptors and signaling pathways	VEGF receptors	Sorafenib, sunitinib, bevacizumab	[139,142-145]
	EGF receptors	Erlotinib, gefitinib, cetuximab	[120-126]
	IGF receptors	IMC-A12	[132-134]
	Hedgehog pathway	Cyclopamine, anti-Rab23, SHH neutralizing antibodies	[107,108]
	Wnt/ β-catenin	Anti-Wnt antibody, AKT1 inhibitor	[34]
	Notch	TW-37	[136]

VEGF: Vascular endothelial growth factor; IGF: Insulin growth factor; EGF: Epidermal growth factor; ABC: ATP binding cassette.