Mechanism of action associated with response to erbB targeted therapy

676 Background: ErbB receptors are associated with aggressive cancers and are therapeutic targets for drugs, such as antibodies or small molecules that block receptor kinase activity and downstream signaling pathways. Nuclear cellular receptors, such estrogen receptor (ER) and progesterone receptor (PR), are also targeted for anti-hormone therapies. There is an inverse correlation between ErbB2 receptor expression and ER and PR. In patients with increased expression levels of ErbB2 anti-hormone therapies are less effective. In addition, the estrogen receptors pathway upregulates the anti-apoptotic factor Bcl2 which is associated with resistance to various therapies. Methods: Breast cancer biopsies from patients treated with small molecule inhibitors to erbB receptors or antibodies were analyzed for ER, PR, Bcl2 and ErbB receptors. In addition, the breast cancer cell line Au-565, that overexpresses ErbB2, was transfected with either ER or Bcl2 cDNAs. The cells were treated with Herceptin or a dual EGFR/Erb...