%0 Journal Article
%T Lapatinib, a Dual-Targeted Small Molecule Inhibitor of Egfr and Her2, in Her2-Amplified Breast Cancer: From Bench to Bedside
%A Roger Y. Tsang
%A Saeed Sadeghi and Richard S. Finn
%J Clinical Medicine Insights: Therapeutics
%D 2012
%I 
%R 10.4137/CMT.S3783
%X The HER-2/neu gene product is a 185 kDa Type I receptor tyrosine kinase which consists of an extracellular domain, transmembrane domain, kinase domain, and cytoplasmic tail. The initial discovery that amplification and subsequent overexpression of the HER-2/neu oncogene plays a pivotal role in the pathogenesis of 20%¨C25% of breast cancers has since led to significant clinical advances in the management of this subtype of breast cancer. The first approved HER2-targeted therapy, trastuzumab, is a humanized monoclonal antibody against the extracellular domain of HER2 and has demonstrated survival benefits in both the metastatic and adjuvant settings. Lapatinib, a small molecule tyrosine kinase inhibitor of both the epidermal growth factor receptor (EGFR) and HER2 is now also approved for advanced HER2-amplified breast cancer and is currently being evaluated in the adjuvant setting. Importantly, lapatinib has been shown to have activity in women with HER2-amplified breast cancer that is refractory to trastuzumab. In addition, it has been shown to extend survival in the front-line setting in combination with letrozole for estrogen receptor (ER) positive, HER2-positive breast cancer. Here we will review the biologic rationale and pre-clinical data that drove its initial clinical development as well as current clinical data and ongoing studies.
%U http://www.la-press.com/lapatinib-a-dual-targeted-small-molecule-inhibitor-of-egfr-and-her2-in-article-a2434