Targeting EGFR and HER2 for Molecular Imaging of Cancer

Abstract

The epidermal growth factor (EGF) receptor (EGFR, HER1, ErbB1) and human epidermal growth factor receptor type 2 (HER2, ErbB2) belong to the ErbB family of type I tyrosine kinases (TKs). This family of receptor TKs also includes another two closely related members HER3/ErbB3 and HER4/ErbB4. The general structure of these cell surface receptor proteins contains an extracellular ligand-binding domain, a hydrophobic transmembrane domain, an intracellular tyrosine kinase domain and a non-catalytic carboxyl terminal tail (Ferguson et al., 2000; Kari et al., 2003; Mitsudomi & Yatabe, 2010; Pines et al., 2010). Various ligands for EGFR, HER3 and HER4 have been identified, with EGF the most extensively characterized for its binding and activation of EGFR. These ErbB proteins are present in the plasma membrane as monomers. Upon ligand binding, the ErbB receptors can associate with each other to form different receptor dimers, which may be homodimers (e.g., EGFR-EGFR) or heterodimers (e.g., EGFR-HER2). The dimerization results in the activation of kinase activity and downstream signaling pathways, which often leads to cell proliferation and malignant tumor growth. HER2 is an exception, with no compatible ligand identified. However, it is the preferred heterodimerization partner for all other ErbB members (Mishani & Hagooly, 2009; Niu et al., 2008; Tzahar et al., 1996; Yarden & Sliwkowski, 2001).