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Highly Accessed Review

HER2 therapy: Molecular mechanisms of trastuzumab resistance

Rita Nahta1 and Francisco J Esteva123

Author Affiliations

1 Department of Breast Medical Oncology, Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Holcombe Blvd, Houston, Texas 77030-4009, USA

2 Department of Molecular and Cellular Oncology, Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Holcombe Blvd, Houston, Texas 77030-4009, USA

3 The University of Texas Graduate School of Biomedical Sciences at Houston, 6767 Bertner Ave, Houston, Texas 77030, USA

Breast Cancer Research 2006, 8:215  doi:10.1186/bcr1612

Published: 6 November 2006

Abstract

Trastuzumab is a monoclonal antibody targeted against the HER2 tyrosine kinase receptor. The majority of patients with metastatic breast cancer who initially respond to trastuzumab develop resistance within one year of treatment initiation, and in the adjuvant setting 15% of patients still relapse despite trastuzumab-based therapy. In this review, we discuss potential mechanisms of antitumor activity by trastuzumab, and how these mechanisms become altered to promote therapeutic resistance. We also discuss novel therapies that may improve the efficacy of trastuzumab, and that offer hope that the survival of breast cancer patients with HER2-overexpressing tumors can be vastly improved.