Clinical activities of the epidermal growth factor receptor family inhibitors in breast cancer
Authors Elizabeth S Henson, James B Johnston, Marek Los, Spencer B Gibson
Published 15 January 2008 Volume 2007:1(3) Pages 229—239
Elizabeth S Henson1, James B Johnston1,2, Marek Los1, Spencer B Gibson1
1Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada 2Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Abstract: The epidermal growth factor (EGF) receptors play an important role in epithelial cell function. Upon stimulation of these receptors, an extensive network of signal transduction pathways is activated, including the PI3K/AKT and Ras/Erk pathways. This activation leads to cellular proliferation and survival. In breast cancer, the EGF receptor, ErbB2 (HER2/neu), can be amplified and over-expressed and this is associated with poor prognosis and drug resistance. Trastuzumab is a monoclonal antibody against ErbB2 and has demonstrated activity in the therapy of breast cancer patients with over-expression of ErbB2, both in the metastatic and adjuvant setting. Recently, a tyrosine kinase inhibitor, lapatinib, that targets both ErbB1 and ErbB2, has also shown activity in metastatic breast cancer. In this review, we will discuss the ErbB receptors and their signaling networks in breast cancer, as well as the clinical activities of trastuzumab and lapatinib in this disease.
Keywords: trastuzumab, lapatinib, ErbB receptors, breast cancer and tyrosine kinases