Liver Cancer: Therapeutic Challenges and the Importance of Experimental Models

Table 2

Main pharmacological characteristics of systemic drugs used in HCC treatment.

Drug	Dose	Family	Molecular target	Reference
First-line drugs
Sorafenib	800 mg/day	Inhibitors of tyrosine kinase receptors (TKRs)	VEGFR-1, VEGFR-2, VEGFR-3, PDGFRβ, RET, c-KIT, and FMS-like tyrosine kinase-3, Ras/MAPK pathway, and wild-type and mutant Raf-1 (C-Raf) and B-Raf	[50, 51]
Lenvatinib	12 mg/day	Inhibitors of TKRs	VEGFR, FGFR 1–4, PDGFR, and SCF	[53–55]
Second-line drugs
Regorafenib	160 mg/day	Inhibitors of TKRs	VEGFR-1, VEGFR-2, VEGFR-3, PDGFRβ, FGFR-1, KIT, RET, RAF1, and BRAF	[56, 57]
Ramucirumab	8 mg/kg every 2 weeks	Human monoclonal antibody (IgG1)	VEGFR-2	[58–60]
Futures therapies
Pirfenidone	300–600 mg/Kg (mouse model)	Pyridones	Induction G0/G1 cycle arrest, inhibition of Wnt/β-catenin signaling pathway, ligand/activator of PPARα and PPARγ; SIRT1/LκB1/pAMPK activation	[65–67]

TKR: tyrosine kinase receptors; VEGFR: vascular endothelial growth factor receptor; PDGFR: platelet-derived growth factor receptor; FGFR: fibroblast growth factor receptor; SCF: steam cell factor; EGF: epidermal factor receptor; PPARα: peroxisome proliferator-activated receptor alpha; PPARγ: peroxisome proliferator-activated receptor gamma; α-SMA: alpha-smooth muscle actin; TGF-β: transforming growth factor-beta; TNF-α: tumor necrosis factor-alpha; COX-2: cyclooxygenase 2; PCNA: proliferating cell nuclear antigen; NF-κB: nuclear factor-κB; SIRT1: sirtuin 1; LκB1: liver kinase B1; and pAMPK: phospho-AMP-activated protein kinase.