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Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer

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Abstract

Trastuzumab (Herceptin®) is currently used as a treatment for patients whose breast tumors overexpress HER2/ErbB2. Trastuzumab-DM1 (T-DM1, trastuzumab emtansine) is designed to combine the clinical benefits of trastuzumab with a potent microtubule-disrupting drug, DM1 (a maytansine derivative). Currently T-DM1 is being tested in multiple clinical trials. The mechanisms of action for trastuzumab include inhibition of PI3K/AKT signaling pathway, inhibition of HER-2 shedding and Fcγ receptor mediated engagement of immune cells, which may result in antibody-dependent cellular cytotoxicity (ADCC). Here we report that T-DM1 retains the mechanisms of action of unconjugated trastuzumab and is active against lapatinib resistant cell lines and tumors.

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Conflict of interest

All authors are employees of Genentech, Inc.

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Authors and Affiliations

  1. Research Oncology, Genentech, Inc., 1 DNA Way, Mailstop 72, South San Francisco, CA, 94080, USA

    Teemu T. Junttila, Guangmin Li, Kathryn Parsons, Gail Lewis Phillips & Mark X. Sliwkowski

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  1. Teemu T. Junttila
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  2. Guangmin Li
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  3. Kathryn Parsons
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  4. Gail Lewis Phillips
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  5. Mark X. Sliwkowski
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Correspondence to Mark X. Sliwkowski.

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Junttila, T.T., Li, G., Parsons, K. et al. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat 128, 347–356 (2011). https://doi.org/10.1007/s10549-010-1090-x

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  • DOI: https://doi.org/10.1007/s10549-010-1090-x

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