T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.
Bottom Line: T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression.T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T.T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy.
Affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, Connecticut, 06520.Show MeSH
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Mentions: Next, we evaluated by cell cycle analysis whether T-DM1 may induce G2/M phase arrest and apoptosis in high HER2-expressing cells. In multiple experiments, we found the percentage of cells in G2/M phase to shift from a mean of 21.85 ± 1.89% in the pretreatment HER2 high expressor cell lines to a mean of 51 ± 8.9% (P = 0.01) after 48–72 h of exposure to 2 μg/mL of T-DM1. T-DM1 showed activity (i.e., induction of G2/M phase arrest and apoptosis) against all USC cell lines tested including cell lines endowed with primary resistance to the cytostatic effects of T. In contrast, no significant G2/M phase arrest was noted in low expressor HER2 cell lines after exposure to T-DM1 (Fig.5).
Affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, Connecticut, 06520.