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Pertuzumab, a humanized monoclonal antibody, is a HER2 dimerization inhibitor for the treatment of metastatic HER2-positive breast cancer.

Trastuzumab and Pertuzumab are highly synergistic inhibitors of BT474 breast cancer cell survival. The combination of trastuzumab and Pertuzumab mediates a loss of up to 60% of cells at doses in which individual drugs do not alter cell survival. The combination of trastuzumab and Pertuzumab reduces the percentage of proliferating (S-phase) cells by more than 2-fold. A combination of trastuzumab and Pertuzumab inhibits cell proliferation and survival to a greater degree than does either agent alone[1].

In Calu-3 NSCLC xenografts, monotherapy with pertuzumab or trastuzumab is able to significantly inhibit tumor growth, with treatment-to-control ratios (TCR) of 0.23 and 0.27, respectively. The combination of trastuzumab and pertuzumab produces a dramatically enhanced antitumor activity compared with single-agent treatments (TCR 0.05, resulting in tumor regression and, in 3 of 10 animals, complete tumor remission). Treatment of KPL-4 breast cancer xenografts with either trastuzumab or pertuzumab inhibits tumor growth with TCRs of 0.67 and 0.65, respectively. Pertuzumab maintains antitumor activity after progression on trastuzumab[2].

[1]. Nahta R, et al. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survivalof breast cancer cells. Cancer Res. 2004 Apr 1;64(7):2343-6. [2]. Scheuer W, et al. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res. 2009 Dec 15;69(24):9330-6.

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