Perspectives on anti-HER monoclonal antibodies.

Abstract

The ability of Herceptin to prolong survival in women with HER2-overexpressing breast tumors has proven the concept of using humanized or chimeric monoclonal antibodies (MAbs) for cancer therapy. MAbs have been developed that are specific for many tumorigenic molecules and receptors. They can potentially be used to treat a range of solid tumors. Among the most promising targets for therapy are members of the human epidermal growth factor receptor (HER/ErbB) family, particularly HER1 and HER2. Several MAbs have been produced that are directed against HER1. One of these agents, cetuximab (Erbitux), is now advanced in clinical development. HER2 is also a key target and methods are being investigated to maximize the effect of using MAbs to inhibit this receptor. One approach aims to augment the efficacy of trastuzumab (Herceptin) by coupling it to a chemotherapeutic agent, thus enabling the delivery of cytotoxic therapy at a cellular level. Another opportunity is based on research that shows that HER2 acts as a dimerization partner for other HER receptors and consequently is important in HER-ligand-dependent tumor growth. Therefore, anti-HER2 MAbs that inhibit the association of HER2 with other HER family members have the potential to be highly effective. This article reviews some of these alternative approaches to MAb-based anti-HER therapy that will hopefully improve treatment outcome for patients with a range of solid tumors.