RT Journal Article
SR Electronic
T1 The HER-2-Targeting Antibodies Trastuzumab and Pertuzumab Synergistically Inhibit the Survival of Breast Cancer Cells
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 2343
OP 2346
DO 10.1158/0008-5472.CAN-03-3856
VO 64
IS 7
A1 Nahta, Rita
A1 Hung, Mien-Chie
A1 Esteva, Francisco J.
YR 2004
UL http://cancerres.aacrjournals.org/content/64/7/2343.abstract
AB 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.