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Trastuzumab: triumphs and tribulations

Oncogene volume 26, pages 3637–3643 (2007)Cite this article

Abstract

The human epidermal growth factor receptor 2 (HER2) tyrosine kinase receptor is overexpressed in approximately 20–30% of human breast cancers, and is associated with reduced survival. Hence, numerous therapeutic strategies have been tested for their ability to target the HER2 protein. The humanized monoclonal antibody trastuzumab (Herceptin) was the first HER2-targeted agent approved for clinical use in breast cancer patients. Response rates to single-agent trastuzumab range from 12 to 34% for metastatic breast cancer (MBC), and significant improvements in survival rates are achieved in patients with early-stage HER2-overexpressing breast cancer in the adjuvant setting. Despite its initial efficacy, acquired resistance to trastuzumab develops in a majority of patients with MBC, and a large subset never responds, demonstrating primary resistance. Molecular mechanisms of trastuzumab antineoplastic activity and potential mechanisms contributing to its resistance will be discussed in this review. Novel agents that may enhance trastuzumab efficacy will also be discussed.

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Acknowledgements

We thank funding from the National Cancer Institute (K01CA118174, R Nahta), the Breast Cancer Research Foundation (FJ Esteva), the University Cancer Foundation at the University of Texas MD Anderson Cancer Center (FJ Esteva, R Nahta), the Nellie B Connally Breast Cancer Research Fund, and NIH Cancer Center Support Grant CA-16672 (Media Preparation Facility and Flow Cytometry facilities).

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Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    R Nahta & F J Esteva

  2. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    F J Esteva

  3. Department of Breast Medical Oncology, Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    R Nahta & F J Esteva

  4. Department of Molecular and Cellular Oncology, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA

    F J Esteva

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Nahta, R., Esteva, F. Trastuzumab: triumphs and tribulations. Oncogene 26, 3637–3643 (2007). https://doi.org/10.1038/sj.onc.1210379

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