In Vitro Study Finds Herceptin and Omnitarg Synergistic

The HER-2-Targeting Antibodies Trastuzumab (Herceptin (tm)) and Pertuzumab (Omnitarg (tm) 2C4) 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.

I believe that this M.D. Anderson in vitro study is quite important. I have been waiting for the Herceptin/Omnitarg combination to be used in a breast cancer context. As you know Herceptin effectively blocks the HER-2 receptor and prevents tumor growth signals the immune system to attack the HER-2 positive cancer cell and works synergistically with chemotherapy.

HER-2 also binds with other members of the HER family (i.e. HER-1/EGFR HER-3 and HER-4) in a process known as heterodimerisation which can lead to cancer cell proliferation. Omnitarg is designed to prevent HER-2 from binding with other HER family members thereby potentially reducing or eliminating cancer cell proliferation.

One theory suggests that some women progress while using Herceptin due to the heterodimerisation process described above. By combining Herceptin and Omnitarg it appears that that two vital extracellular functions of the HER-2 receptor are blocked. This combination may benefit a larger number of HER-2 positive breast cancer patients in the future. Keep an eye on this drug combination as it progresses into further testing.