The anti-EGFR monoclonal antibody blocks cisplatin-induced activation of EGFR signaling mediated by HB-EGF

Abstract 

Cisplatin is a key agent in combination chemotherapy for various types of solid tumor. We now show that cisplatin activates signaling by the epidermal growth factor receptor (EGFR) by inducing cleavage of heparin-binding epidermal growth factor-like growth factor (HB-EGF). Matuzumab, a monoclonal antibody to EGFR, inhibited cisplatin-induced EGFR signaling, likely through competition with the soluble form of HB-EGF for binding to EGFR. Matuzumab enhanced the antitumor effect of cisplatin in nude mice harboring human non-small cell lung cancer xenografts. Our findings shed light on the mechanism by which monoclonal antibodies to EGFR might augment the efficacy of cisplatin.

Abbreviations: EGF, epidermal growth factor, EGFR, EGF receptor, mAb, monoclonal antibody, NSCLC, non-small cell lung cancer, HB-EGF, heparin-binding EGF-like growth factor, HRP, horseradish peroxidase, TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling

Keywords: EGF receptor, Heparin-binding EGF-like growth factor, Matuzumab, Cisplatin, Non-small cell lung cancer