Journal of Cancer Research and Therapeutics Close
 

Figure 3:Mechanistic representation of epidermal growth factor receptor signaling and inhibition by anti-epidermal growth factor receptor antibody and small molecule inhibitors. There are 11 ligands (EGF, TGFα), HB EGF-like growth factor, amphiregulin, beta-cellulin, epiregulin, and epigen known to bind and activate epidermal growth factor receptor. Ligand binding to epidermal growth factor receptor on the cell surface induces receptor dimerization and cross-phosphorylation of the cytoplasmic tyrosine kinase domain, which triggers downstream signaling through effector and adaptor proteins. The principal pathways included are (1) RAS/RAF/MEK, (2) PI3K/AKT, and (3) JAK/STAT, pathways resulting in cell proliferation, invasion, migration, and inhibition of apoptosis. The anti-epidermal growth factor receptor antibody or small molecule inhibitors are used as targeted therapy where overexpression or actionable mutations are present in epidermal growth factor receptor gene, respectively. EGF = epidermal growth factor, EGFR = Epidermal growth factor receptor, JAK = Janus kinase, MAPK = Mitogen-activated protein kinase, MEK = MAPK/extracellular signal-regulated kinase kinase, mTOR = Mammalian target of rapamycin, PI3K = Phosphatidylinositol-3 kinase, STAT = Signal transducer and activator of transcription, TGFα = Transforming growth factor α, HB = Heparin binding

Figure 3:Mechanistic representation of epidermal growth factor receptor signaling and inhibition by anti-epidermal growth factor receptor antibody and small molecule inhibitors. There are 11 ligands (EGF, TGFα), HB EGF-like growth factor, amphiregulin, beta-cellulin, epiregulin, and epigen known to bind and activate epidermal growth factor receptor. Ligand binding to epidermal growth factor receptor on the cell surface induces receptor dimerization and cross-phosphorylation of the cytoplasmic tyrosine kinase domain, which triggers downstream signaling through effector and adaptor proteins. The principal pathways included are (1) RAS/RAF/MEK, (2) PI3K/AKT, and (3) JAK/STAT, pathways resulting in cell proliferation, invasion, migration, and inhibition of apoptosis. The anti-epidermal growth factor receptor antibody or small molecule inhibitors are used as targeted therapy where overexpression or actionable mutations are present in epidermal growth factor receptor gene, respectively. EGF = epidermal growth factor, EGFR = Epidermal growth factor receptor, JAK = Janus kinase, MAPK = Mitogen-activated protein kinase, MEK = MAPK/extracellular signal-regulated kinase kinase, mTOR = Mammalian target of rapamycin, PI3K = Phosphatidylinositol-3 kinase, STAT = Signal transducer and activator of transcription, TGFα = Transforming growth factor α, HB = Heparin binding