Figure 2.

Association and inhibition of EGFR and VEGF pathways. EGFR is activated when EGF and TGF-α bind to it and is involved in the growth, proliferation and differentiation of tumor cells through the conduction of downstream pathways. After EGFR activation, HIF-1 can be upregulated, resulting in VEGF gene expression. HIF-1, IL-8, bFGF and PDGF can promote the release of VEGF by tumors, thereby activating the VEGF pathway and promoting the formation of new blood vessels. Drugs targeting the EGFR and VEGF pathways are also used clinically, including EGFR inhibitors and VEGF-2 inhibitors. EGFR binds to the intracellular domain of EGFR cell TKIs (erlotinib, gefitinib, icotinib, dacomitinib, afatinib, almonertinib and osimertinib). Mechanisms of VEGF inhibitors include interference with VEGF (bevacizumab), binding to VEGFR-2 intracellular domains (nintedanib and cediranib) and interfering with VEGFR-2 extracellular domains (ramucirumab). The use of EGFR inhibitors can downregulate HIF-1 expression, but the activation of the VEGF pathway is affected by a variety of factors, so EGFR inhibitors alone are not effective in the treatment of advanced non-small cell lung cancer. TKI, tyrosine kinase inhibitor; HIF-1, hypoxia-inducible factor.