title: Recent progress in protein-protein interaction study for EGFR-targeted therapeutics.
abstract: Epidermal growth factor receptor (EGFR) expression is upregulated in many tumors and its aberrant signaling drives progression of many cancer types. Consequently, EGFR has become a clinically validated target as extracellular tumor marker for antibodies as well as for tyrosine kinase inhibitors. Within the last years, new mechanistic insights were uncovered and, based on clinical experience as well as progress in protein engineering, novel bio-therapeutic approaches were developed and tested.
  
  
  
  The potential therapeutic targeting arsenal in the fight against cancer now encompasses bispecific or biparatopic antibodies, DARPins, Adnectins, Affibodies, peptides and combinations of these binding molecules with viral- and nano-particles. We review past and recent binding proteins from the literature and include a brief description of the various targeting approaches. Special attention is given to the binding modes with the EGFR. Expert commentary: Clinical data from the three approved anti EGFR antibodies indicate that there is room for improved therapeutic efficacy. Having choices in size, affinity, avidity and the mode of EGFR binding as well as the possibility to combine various effector functions opens the possibility to rationally design more effective therapeutics.
authors.affiliation: a Cellular and Molecular Biotechnology group, Faculty of Technology , Bielefeld University , Bielefeld , Germany.
authors.forename: Rebecca Christine
authors.initials: RC
authors.lastname: Feiner
authors.affiliation: a Cellular and Molecular Biotechnology group, Faculty of Technology , Bielefeld University , Bielefeld , Germany.
authors.forename: Kristian Mark
authors.initials: KM
authors.lastname: Müller
mesh_terms: D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011485:Protein Binding; D060066:Protein Interaction Maps / Q000187:drug effects / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020543:Proteome / Q000187:drug effects / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047428:Protein Kinase Inhibitors; D020543:Proteome; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGF-R; ErbB1; antibody; antigen-binding scaffolds; cancer targeting; tumor targeting; virus-like particles