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

Takeshi Yoshida; Isamu Okamoto; Tsutomu Iwasa; Masahiro Fukuoka; Kazuhiko Nakagawa

doi:10.1016/j.febslet.2008.11.010

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

Takeshi Yoshida, Isamu Okamoto, Tsutomu Iwasa, Masahiro Fukuoka, Kazuhiko Nakagawa

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

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. Crown

Original language	English
Pages (from-to)	4125-4130
Number of pages	6
Journal	FEBS Letters
Volume	582
Issue number	30
DOIs	https://doi.org/10.1016/j.febslet.2008.11.010
Publication status	Published - Dec 24 2008
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2008.11.010

Cite this

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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. Crown",

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AU - Yoshida, Takeshi

AU - Okamoto, Isamu

AU - Iwasa, Tsutomu

AU - Fukuoka, Masahiro

AU - Nakagawa, Kazuhiko

PY - 2008/12/24

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AB - 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. Crown

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

Abstract

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