Implications of biomarkers in human hepatocellular carcinoma pathogenesis and therapy

Table 1 Several important molecular-targeted therapies that inhibit the vascular endothelial growth factor/vascular endothelial growth factor receptor signaling pathways involved in hepatocellular carcinoma

Names of drug	Targeted signaling pathways	Phase/number of patients	Main side effects and prevalence	Efficiency (mo) (PFS/OS)
Sorafenib	Raf/MAPK/ERK, VEGFR-2, -3, PDGFR	II/137	Diarrhea (8%), hand-foot skin reaction (5%)	5.5/9.2[49]
Bevacizumab	VEGF/VEGFR	II/46	Hypertension (15%), thrombosis (6%), and major bleeding (11%)	6.9/12.4[52]
Sunitinib	VEGFR1, VEGFR2, PDGFR, c-KIT, FLT3, RET kinases	II/45	Fatigue (62%), diarrhea (47%), nausea (44%)	1.5/9.3[54]
Brivanib	VEGFR, FGFR	II/55	Hypertension (33.8%), proteinuria (14.7%), hemorrhage (11.8%)	2.7/10[56]
Linifanib	VEGFR and PDGFR	II/44	Hypertension (25.0%) and fatigue (13.6%)	3.7/9.7[58]
Ramucirumab	VEGFR-2	II/40	Hypertension (14%), gastrointestinal hemorrhage and infusion-related reactions (7% each), and fatigue (5%)	4.0/12[59]

VEGFR: Vascular endothelial growth factor receptor; ERK: Extracellular regulated protein kinases; MAPK: Mitogen-activated protein kinase; PDGFR: Platelet-derived growth factor receptor; FGFR: Fibroblast growth factor receptor; PFS: Progression-free survival; OS: Overall survival.