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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.

Authors: Gril, Brunilde  Vidal, Michel  Assayag, Franck  Poupon, Marie-France  Liu, Wang-Qing  Garbay, Christiane 
Citation: Gril B, etal., Int J Cancer. 2007 Jul 15;121(2):407-15. doi: 10.1002/ijc.22674.
Pubmed: (View Article at PubMed) PMID:17372910
DOI: Full-text: DOI:10.1002/ijc.22674

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.


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RGD Object Information
RGD ID: 13504751
Created: 2018-01-22
Species: All species
Last Modified: 2018-01-22
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.