Integration of Target-Based Agents in Current Protocols of Breast Cancer Therapy

Abstract

Breast cancer is a heterogeneous disease sustained by the dysregulation of numerous molecular pathways, such as cell cycle progression, angiogenesis, and apoptosis. Recent progress in molecular technology has allowed better characterization of the transformed phenotype, identifying molecular features that distinguish tumor from normal tissue and represent rational targets for more selective therapeutic approaches. In this chapter, we focus on the molecular target-based agents in the most advanced state of clinical development in breast cancer. Trastuzumab, a monoclonal antibody with high specificity for the HER2 protein, is the first targeted agent approved for the treatment of metastatic and early breast cancer. Bevacizumab, a monoclonal antibody directed against the VEGF-A ligand, with antiangiogenetic properties, and lapatinib, a dual tyrosine-kinase inhibitor of both EGFR and HER2, have been recently approved for use in the treatment of metastatic breast cancer. Several other compounds directed against different targets have also entered clinical evaluation. Key issues in the clinical development of targeted therapy include the proper selection of patients, the identification of the optimal combinations with conventional treatments, predictive markers of activity and toxicity, and the most appropriate therapeutic strategies.