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.

• Authors: Takeshi Yoshida, Isamu Okamoto, Tsutomu Iwasa, Masahiro Fukuoka, Kazuhiko Nakagawa
• Journal: FEBS letters (FEBS Lett) Vol. 582 Issue 30 Pg. 4125-30 (Dec 24 2008) ISSN: 1873-3468 [Electronic] England
• PMID: 19027738 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• HBEGF protein, human
• Hbegf protein, mouse
• Heparin-binding EGF-like Growth Factor
• Intercellular Signaling Peptides and Proteins
• EGFR protein, human
• ErbB Receptors
• matuzumab
• Cisplatin

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (pharmacology)
• Cisplatin (pharmacology)
• ErbB Receptors (agonists, antagonists & inhibitors, metabolism)
• Female
• Heparin-binding EGF-like Growth Factor
• Humans
• Intercellular Signaling Peptides and Proteins (metabolism)
• Lung Neoplasms (metabolism)
• Mice
• Mice, Nude
• Small Cell Lung Carcinoma (metabolism)
• Xenograft Model Antitumor Assays