Resistance to HER2-targeted therapy

Abstract

Production and approval of trastuzumab (Herceptin®) for the treatment of metastatic breast cancer (MBC) was a millstone in antibody-based targeted therapy in the cancer treatment. However, despite the early success in the clinical trials, trastuzumab failed to appreciate the initial attraction due to development of resistance to the drug. The majority of patients who benefit from the drug acquire resistance to it and experience tumor recurrence within 1 year. Several molecular and cellular mechanisms underlying the resistance to trastuzumab have been proposed. In this review, first, we provide a brief history leading to production of trastuzumab. Also we consider the cellular and molecular antitumor effects of trastuzumab and then, we discuss the mechanisms underlying trastuzumab resistance in four levels.

Keywords

• Trastuzumab
• ErbB
• Breast cancer
• Mechanisms of action
• Resistance