Sensitization of chemotherapy by anti-HER

This article reviews the current state of efforts targeting human epidermal growth factor receptor-2 (erbB2/HER2)in breast cancer therapy. The results of recently conducted clinical studies with trastuzumab and several other compounds are presented. Trastuzumab, a humanised monoclonal antibody(mAb)directed against the extracellular domain of HER2, has been shown to be active against HER2-overexpressing metastatic breast cancer, either as a single agent or when used in combination with chemotherapy. In preclinical models, trastuzumab has shown additive and even synergistic anti-tumor activity with the chemotherapeutic agents. In a large, randomised, phase III trial, the combination of trastuzumab and chemotherapy was shown to improve the response rate and survival in patients with metastatic breast cancer. The high incidence of cardiotoxicity seen with the combination of trastuzumab plus anthracycline drugs prompted several clinical studies combining trastuzumab with other chemotherapeutic agents, including taxanes, vinorelbine and platinum salts. This article summarises the available data on trastuzumab-based combination chemotherapies and novel drugs targeting HER2 and signal transduction molecules for the treatment of breast cancer.