Systemic treatment of liver cancer: Current status and future perspectives

Table 2 Correlation between targets and pathogenesis of diseases

Target category	Related signaling pathways	Pathogenesis of the disease	Representative drugs
Angiogenesis targets	VEGF/VEGFR, PDGFR, FGFR	Excessive tumor angiogenesis promotes tumor growth and metastasis	Sorafenib, lenvatinib, donafenib
Proliferation-related targets	Raf/MEK/ERK, MET, RET	Abnormally activated proliferation signals (such as Raf mutations and MET amplifications) drive tumor progression	Sorafenib, cabozantinib, donafenib
Targets related to drug resistance/metastasis	AXL, ROS1, NTRK	Mediate tumor drug resistance (such as resistance to EGFR inhibitors) and metastatic spread	Cabozantinib
Regulation of immune microenvironment	STAT3, PD-1 cooperative pathway	The immunosuppressive state in the tumor microenvironment (for example, the activation of STAT3 inhibits the activity of immune cells)	Donafenib, sorafenib

PD-1: Programmed cell death protein 1; VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor; Raf kinase: Rapidly accelerated fibrosarcoma kinase; MEK: Mitogen-activated protein kinase kinase; ERK: Extracellular signal-regulated kinase; FGFR: Fibroblast growth factor receptor; RET: RET Proto-oncogene, receptor tyrosine kinase; MET: Mesenchymal-epithelial transition factor, receptor tyrosine kinase; AXL: AXL receptor tyrosine kinase; ROS1: ROS1 proto-oncogene, receptor tyrosine kinase; NTRK: Neurotrophin receptor tyrosine kinase; PDGFR: Platelet-derived growth factor receptor; EGFR: Epidermal growth factor receptor; STAT3: Signal transducer and activator of transcription 3.