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ABSTRACT: Trastuzumab has been found to have potent antiproliferative effects in human epidermal growth factor receptor 2 (HER-2)-overexpressing human breast tumors. Inhibition of vascular endothelial growth factor receptor (VEGFR), a protein often overexpressed in breast carcinoma, has been shown to induce apoptosis.
Breast carcinoma cell lines were cultured with increasing doses of trastuzumab and/or a VEGFR tyrosine kinase inhibitor (TKI). Growth inhibition and apoptosis were assessed after 5 days and 48 hours of treatment, respectively. Combination index values were calculated to determine the effectiveness of this drug combination.
A dose-dependent growth inhibition was shown in all cell lines tested with the VEGFR TKI, whereas trastuzumab was effective only in the HER-2-positive cells. A synergistic interaction was shown in the HER-2-overexpressing cell lines, accompanied by an increase in apoptosis.
The combination of trastuzumab and a VEGFR TKI may be of therapeutic value in select breast cancer patients.
American journal of surgery 04/2009; 197(3):331-6. · 2.36 Impact Factor