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Annals of Oncology Advance Access published online on October 11, 2005
Annals of Oncology, doi:10.1093/annonc/mdi405
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© 2005 European Society for Medical Oncology
Received May 31, 2005
Revised July 29, 2005
Accepted August 2, 2005

Original article

Selective inhibition of HER2 inhibits AKT signal transduction and prolongs disease-free survival in a micrometastasis model of ovarian carcinoma

J. P. Delord 1*, C. Allal 2, M. Canal 2, E. Mery 2, P. Rochaix 1, I. Hennebelle 2, A. Pradines 2, E. Chatelut 1, R. Bugat 1, S. Guichard 1, and P. Canal 2

1 Groupe de Pharmacologie clinique et expérimentale des médicaments anti cancéreux (EA 3035), Institut Claudius Regaud, Toulouse, France; Université Paul Sabatier, Toulouse, France
2 Groupe de Pharmacologie clinique et expérimentale des médicaments anti cancéreux (EA 3035), Institut Claudius Regaud, Toulouse, France

* To whom correspondence should be addressed.
J. P. Delord, E-mail: delord_j{at}icr.fnclcc.fr


  Abstract

Although first-line chemotherapy induces complete clinical remission in many cases of epithelial ovarian cancer, relapse usually occurs 18-28 months from diagnosis owing to micrometastases. The present study aimed to evaluate the effect of trastuzumab on disease-free and overall survival in a specially designed murine model of ovarian cancer (OVCAR-3), which mimicked the natural history of human micrometastatic disease. Trastuzumab can cure the mice if started soon after induction chemotherapy. It can modestly inhibit the proliferation through mitogen-activated protein kinase signal transduction and clearly inhibit AKT phosphorylation, which is involved in survival pathway. As OVCAR-3 cell lines show no HER2 amplification or overexpression, these results warrant further studies to assess the efficacy of trastuzumab in the early stage of relapse in cancer models other than those overexpressing HER2.

Keywords: antineoplastic drugs; disease-free; experimental animal models; ovarian carcinoma; survival; trastuzumab.
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[Abstract] [Full Text] [PDF]


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