The Tyrosine Kinase Inhibitor ZD1839 ("Iressa") Inhibits HER2-driven Signaling and Suppresses the Growth of HER2-overexpressing Tumor Cells

摘要: The epidermal growth factor receptor (EGFR) is commonly overexpressed in many human tumors and provides a new target for anticancer drug development. ZD1839 ("Iressa"), quinazoline tyrosine kinase inhibitor selective the EGFR, has shown good activity preclinical studies early phase of clinical trials. However, because it remains unclear which tumor types are best targets treatment with this agent, molecular characteristics that correlate sensitivity to have been studied. In panel breast cancer other epithelial cell lines, HER2-overexpressing were particularly sensitive ZD1839. Growth inhibition these lines was associated dephosphorylation HER2, HER3, accompanied by loss association HER3 phosphatidylinositol 3-kinase, down-regulation Akt activity. These suggest susceptible HER family signaling novel strategies treat aggressive tumors.