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[Cancer Research 64, 2343-2346, April 1, 2004]
© 2004 American Association for Cancer Research

Advances in Brief

The HER-2-Targeting Antibodies Trastuzumab and Pertuzumab Synergistically Inhibit the Survival of Breast Cancer Cells

Rita Nahta1, Mien-Chie Hung2 and Francisco J. Esteva1,2

1 Departments of Breast Medical Oncology, and 2 Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Trastuzumab (herceptin) and pertuzumab (Omnitarg, 2C4) are recombinant humanized monoclonal antibodies that target different extracellular regions of the HER-2 tyrosine kinase receptor. We explored combination effects of these agents in the HER-2-overexpressing BT474 breast cancer cell line. Trastuzumab and 2C4 synergistically inhibited the survival of BT474 cells, in part, because of increased apoptosis. Trastuzumab increased 2C4-mediated disruption of HER-2 dimerization with the epidermal growth factor receptor and HER-3. Combination drug treatment reduced levels of total and phosphorylated HER-2 protein and blocked receptor signaling through Akt but did not affect mitogen-activated protein kinase. These results suggest that combining HER-2-targeting agents may be a more effective therapeutic strategy in breast cancer rather than treating with a single HER-2 monoclonal antibody.




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Copyright © 2004 by the American Association for Cancer Research.