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Breast Cancer Research and Treatment

, Volume 128, Issue 2, pp 347–356 | Cite as

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

  • Teemu T. Junttila
  • Guangmin Li
  • Kathryn Parsons
  • Gail Lewis Phillips
  • Mark X. SliwkowskiEmail author
Preclinical study

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.

Keywords

Breast cancer HER2 ErbB2 Trastuzumab Therapeutic antibodies Antibody drug conjugate (ADC) Trastuzumab-DM1 (T-DM1) 

Notes

Conflict of interest

All authors are employees of Genentech, Inc.

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Teemu T. Junttila
    • 1
  • Guangmin Li
    • 1
  • Kathryn Parsons
    • 1
  • Gail Lewis Phillips
    • 1
  • Mark X. Sliwkowski
    • 1
    Email author
  1. 1.Research OncologyGenentech, Inc.South San FranciscoUSA

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