Recent progress in protein-protein interaction study for EGFR-targeted therapeutics

ABSTRACT

Introduction: 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.

Areas covered: 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.

KEYWORDS:

• ErbB1
• EGF-R
• tumor targeting
• cancer targeting
• antibody
• antigen-binding scaffolds
• virus-like particles

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded