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Annals of Oncology Advance Access originally published online on October 11, 2005
Annals of Oncology 2005 16(12):1889-1897; doi:10.1093/annonc/mdi405
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© 2005 European Society for Medical Oncology

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

J. P. Delord1,2,*, C. Allal1, M. Canal1, E. Mery1, P. Rochaix1,2, I. Hennebelle1, A. Pradines1, E. Chatelut1,2, R. Bugat1,2, S. Guichard1,2 and P. Canal1

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

* Correspondence to: Dr J. P. Delord, Institut Claudius-Regaud, 20–24 rue du Pont Saint Pierre, 31052 Toulouse, France. Tel: +33-5-61-42-41-74; Fax: +33-5-61-42-42-44; E-mail: delord_j{at}icr.fnclcc.fr

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.

Key words: antineoplastic drugs, disease-free, experimental animal models, ovarian carcinoma, survival, trastuzumab


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