<qa>  What is the signaling molecule Akt important in the cell survival pathway?Data are now emerging that Erb-B2 modulates cellular p27 and cyclin D1 protein levels through both RasMAP kinase and PI3KAkt signaling. Reversible interruption of Erb-B2 function by trastuzumab Herceptin has been shown to inhibit MAPk and reduce MAPk-mediated transcription through cyclin D1. In addition, the signaling molecule Akt is important in the cell survival pathway. Akt inhibits apoptosis and is present in the PI3 kinase pathway, which is activated by the EGF family and the IGF family. Several biologic arguments support the use of EGR inhibitors to block HER2 signaling. In HER2-overexpressing cell lines, the HER2 receptor is constitutively phosphorylated. This suggests that HER2 may be transactivated through ligand-stimulated EGFR, also present in tumor cells. In addition, overexpression of HER2 enhances the binding of EGFR ligands to the receptor and potentiates EGFR signaling. HER2 inactivation has been shown to impair EGFR- mediated transformation, and conversely EGFR blocking antibodies can augment the growth inhibitory effect of antiHER2 antibodies in cells with high levels of HER2. Taken together, these data suggest that EGFRHER2 crosstalk is present in a subset of human tumors and that interruption of EGFR may reduce HER2 signaling. Cell cycle progression is regulated predominantly by cyclin-dependent kinases CDKs, which in turn are controlled by a family of CDK inhibitory proteins that include P27KIP1 and P21CIP1-WAF1. Pathways involving CDK inhibitors are commonly destructive in cancer cells. ZD1839 is an orally active, selective EGFR tyrosine kinase inhibitor that blocks signal transduction pathways implicated in cancer cell proliferation, survival, and other host-dependent processes promoting cancer growth. 