Hepatocellular carcinoma and multidrug resistance: Past, present and new challenges for therapy improvement

Table 1 Molecular targeted therapy

Type of drug	Drug	Target	Stage of use (for HCC)
Inhibitors of angiogenesis	Sorafenib1	VEGFR members	Approved
		PDGFR-β
		Flt-3
		FGFR-1
		Raf/MAPK/ERK signaling pathway
	Bevacizumab	VEGFR members	Phase II
	Sunitinib	VEGFR members	Phase II
		PDGFR-α
		PDGFR-β
		Flt-3
		c-Kit
		RET kinases
	Pazopanib	VEGFR members	Phase I
		PDGFR-α
		PDGFR-β
		c-Kit
	Brivanib	VEGF signaling pathway	Phase II
		FGF signaling pathway
	Axitinib	VEGFR members	Phase II/III
		PDGFR-α
		PDGFR-β
		c-Kit
	Linifanib	VEGF	Phase II
		PDGFR-α
		PDGFR-β
	TSU-68	VEGFR-2	Phase II
		PDGFR-α
		PDGFR-β
		FGFR-1
		c-Kit
		Flk-1
	Foretinib	VEGFR-2	Phase I/II
		c-Met
	Dovitinib	VEGFR members	Phase I/II
		PDGFR-β
		FGFR members
		Flt-3
		c-Kit
	Ramucirumab	VEGFR-2	Phase II
Inhibitors of EGFR	Erlotinib	EGFR/HER-1	Phase II
	Lapatinib	EGFR/HER-1	Phase II
		HER-2/NEU
	Gefitinb	EGFR/HER-1	Phase I
	Cetuximab	EGFR/HER-1	Phase II
Inhibitors of the mTOR pathway	Rapamycin	PI3K/Akt/mTOR pathway	Phase I/II
	Everolimus	PI3K/Akt/mTOR pathway	Phase I/II

¹Sorafenib also induces apoptosis and autophagy. HCC: Hepatocellular carcinoma; VEGFR: Vascular endothelial growth factor receptors; Flt-3: Fms-like tyrosine kinase-3; FGFR-1: FGF receptor-1; MAPK: Ras-Raf-mitogen-activated protein kinase; EGFR: Epidermal growth factor receptors; FGF: Fibroblast growth factor; PDGFR: Platelet-derived growth factor receptors; RET: Rearranged during transfection; HER-1: Human epidermal growth factor receptor-1; mTOR: Mammalian target of rapamycin.