Novel Therapeutic Strategies and Combinations for HER2-Overexpressing Breast Cancer

摘要: Approximately 20-30% of breast cancers show increased expression the HER2 receptor tyrosine kinase. Elevated levels are associated with aggressive disease, high metastatic potential, and reduced survival versus other cancer subtypes (Slamon, 1987). Trastuzumab (Herceptin) is a monoclonal antibody targeted against an extracellular region (Carter, 1992). Clinical trials have shown that 15-30% patients HER2overexpressing respond to single-agent trastuzumab for median duration approximately 10 months (Baselga, 1996; Cobleigh, 1999). Response rates improve when combined chemotherapy in (Esteva, 2002; Slamon, 2001). A subset trastuzumab-resistant dual EGFR/HER2 kinase inhibitor lapatinib, although majority (70% or more) primary resistance (Geyer, 2006). Similar treatment, clinical lapatinib indicated response heavily pre-treated, trastuzumab-refractory population was less than one year Hence, clinically available HER2-targeted agents major concern treatment cancer.