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HB‐EGF orchestrates the complex signals involved in triple‐negative and trastuzumab‐resistant breast cancer
Author(s) -
Yotsumoto Fusanori,
Oki Eiji,
Tokunaga Eriko,
Maehara Yoshihiko,
Kuroki Masahide,
Miyamoto Shingo
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25472
Subject(s) - trastuzumab , triple negative breast cancer , breast cancer , medicine , oncology , cancer research , cancer
A number of therapeutic strategies targeting epidermal growth factor receptor (EGFR) have not always led to success in the present state of breast cancer therapy. Notably, there is currently no way to treat trastuzumab‐resistant and triple‐negative breast cancer (TNBC). Here, we found that heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF), a member of the EGFR ligands, was predominantly expressed in breast cancer and that treatment with crossreacting material 197 (CRM197), a specific inhibitor of HB‐EGF, blocked ERK as well as AKT activation via complexes of EGFR and unknown growth factor receptors in TNBC or through complexes of EGFR and human epidermal growth factor receptor‐2 in trastuzumab‐resistant breast cancer, caused significant cell apoptosis and inhibited tumor growth. Accordingly, we can provide a novel concept that a certain EGFR ligand is recognized as a rational target against breast cancer. In addition, it is plausible that CRM197 could be an effective anticancer agent for molecularly targeted therapies.