Her-2 targeted therapy: Beyond breast cancer and trastuzumab

Her-2 is a validated therapeutic target in breast cancer. The two critical questions that remain regarding Her-2 targeting concern 1) the relevance of Her-2 inhibition in other malignancies and 2) the ability of novel agents to achieve greater Her-2 inhibition than trastuzumab. The contribution of cell signaling effects and immunologic mechanisms to the effect of trastuzumab in vivo remains poorly understood. Thus, the preclinical data that support the greater efficacy of novel Her-2 antibodies or small molecule tyrosine kinase inhibitors remain to be validated in clinical trials. In this review, we discuss the evidence from recent trastuzumab clinical trials as a point of departure for consideration of novel Her-2 targeted therapies. Preliminary results from early clinical trials suggest that Her-2 tyrosine kinase inhibitors may extend the population for which this strategy offers therapeutic effect.