title: Anti-EGFR monoclonal antibody in cancer treatment: in vitro and in vivo evidence
abstract: The complexity of EGFR signaling network suggests that the receptor could be promising targets for new personalised therapy. In clinical practice two strategies targeting the receptor are available; they utilise monoclonal antibodies, directed towards the extracellular domain of EGFR, and small molecule tyrosine kinase inhibitors, which bind the catalytic kinase domain of the receptor. In this review, we summarise currently known pre-clinical data on the antitumor effects of monoclonal antibodies, which bind to EGFR in its inactive configuration, competing for ligand binding and thereby blocking ligand-induced EGFR tyrosine kinase activation. As a consequence of treatment, key EGFR-dependent intracellular signals in cancer cells are affected. Data explaining the mechanisms of action of anti-EGFR monoclonal antibodies, currently used in clinical setting and under development for the treatment of solid tumors, are revised with the aim to provide an overview of the most important preclinical studies showing the impact of this class of EGFR targeted agents on tumor biology.
authors.affiliation: Clinical Experimental Oncology Laboratory, National Cancer Institute Giovanni Paolo II, Via Hahnemann 10, 70126 Bari, Italy.
authors.forename: Anna Elisa
authors.initials: AE
authors.lastname: Quatrale
authors.forename: Daniela
authors.initials: D
authors.lastname: Petriella
authors.forename: Letizia
authors.initials: L
authors.lastname: Porcelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colucci
authors.forename: Angelo
authors.initials: A
authors.lastname: Angelo
authors.forename: Amalia
authors.initials: A
authors.lastname: Azzariti
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077544:Panitumumab; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; C527969:necitumumab; D000077544:Panitumumab; C501466:nimotuzumab; C546618:zalutumumab; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C520777:matuzumab; D000068818:Cetuximab