ErbB family receptor inhibitors as therapeutic agents in breast cancer: Current status and future clinical perspective

Breast cancer is the most common cancer diagnosed in women and the second most common cause of female cancer-related deaths, with more than one million new cases diagnosed per year throughout the world. With the recent advances in the knowledge of cellular processes and signaling pathways involved in the pathogenesis of breast cancer, the current focus of researchers and clinicians is to develop novel treatment strategies that can be included in the armamentarium against breast cancer. With the failure of endocrine-targeted therapy and the development of resistance to existing chemotherapy, the most explored pathway as next generation target for breast cancer therapy has been the epidermal growth factor receptor (EGFR) (ErbB-1)/herceptin-2 (HER-2) (ErbB-2) pathway. This review focuses on the rationale for targeting members of ErbB receptor family and numerous agents that are in use for inhibiting the pathway. The mechanism of action, preclinical and clinical trial data of the agents that are in use for targeting the EGFR/HER-2 pathway and the current status, thereof, have been discussed in detail. In addition, the future clinical trial promises these agents hold either as monotherapy or as combination therapy with conventional agents or with other antisignaling agents have been pondered, so as to provide better and more efficacious treatment strategies for breast cancer patients. (C) 2010 Wiley Periodicals, Inc. Med Res Rev 32:166-215, 2012