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Grb2‐SH3 ligand inhibits the growth of HER2 + cancer cells and has antitumor effects in human cancer xenografts alone and in combination with docetaxel
Author(s) -
Gril Brunilde,
Vidal Michel,
Assayag Franck,
Poupon MarieFrance,
Liu WangQing,
Garbay Christiane
Publication year - 2007
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.22674
Subject(s) - docetaxel , cancer research , skbr3 , grb2 , cancer , prostate cancer , medicine , signal transducing adaptor protein , cancer cell , receptor , human breast
HER2 represents an important signaling pathway in breast and other cancers. Herceptin has demonstrated clinical activity, but resistance is common. Thus, new therapeutic approaches to the HER2 pathway are needed. Grb2 is an adaptor protein involved in Ras‐dependent signaling induced by HER2 receptors. A specific Grb2‐SH3 ligand, designed and synthesized in our laboratory, called peptidimer‐c, inhibited colony formation in HER2 overexpressing SKBr3 cancer cells. Combined treatment of peptidimer‐c with docetaxel further inhibited both colony formation and tumor cell survival compared to docetaxel treatment alone. Efficacy of this combined treatment was correlated with a reduction in the phosphorylation of MAPK and AKT. Finally, peptidimer‐c reduced the growth of a HER2 + human breast cancer (BK111) xenograft in nude mice and potentiated the antitumor effect of docetaxel in a HER2+ hormone‐independent human prostate adenocarcinoma (PAC120 HID28) xenograft. These results validate Grb2 as a new target for the HER2 pathway. © 2007 Wiley‐Liss, Inc.