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The anti‐EGFR monoclonal antibody blocks cisplatin‐induced activation of EGFR signaling mediated by HB‐EGF
Author(s) -
Yoshida Takeshi,
Okamoto Isamu,
Iwasa Tsutomu,
Fukuoka Masahiro,
Nakagawa Kazuhiko
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.11.010
Subject(s) - cisplatin , epidermal growth factor receptor , monoclonal antibody , epidermal growth factor , cancer research , chemistry , heparin binding egf like growth factor , antibody , receptor , chemotherapy , biology , immunology , medicine , biochemistry
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.