Fig. 1.

HER2 signaling and targeting agents. a HER2 antigen comprises an extracellular region (I–IV), a transmembrane region and an intracellular tyrosine kinase region. EGFR ligands interact to binding sites of the receptors which is followed by inducing receptor homo- or heterodimerization, C terminus phosphorylation and activation of the cytoplasmic tyrosine kinase for inducing downstream MAPK and PI3K/Akt signaling pathways. b According to HER2 structure and function, immuno therapeutic agents have been developed to target ECD I (e.g., DARPin), II (e.g., pertuzumab), IV (e.g., trastuzumab and ADAPT₆), and tyrosine kinase region (e.g., lapatinib). ECD extracellular domain, MAPK mitogen-activated protein kinases, PI3K phosphatidylinositol-3-kinase