Predicting Sensitivity of Non–Small-Cell Lung Cancer to Gefitinib: Is There a Role for P-Akt?

摘要: The epidermal growth factor receptor (EGFR) is a tyrosine kinase of the ErbB family that abnormally activated in epithelial tumors (1). Receptor activation leads to recruitment and phosphorylation downstream intracellular substrates. Multiple pathways are activated, including phosphatidylinositol 3–kinase/Akt (PI3K/Akt) cascade implicated cell survival RAS/RAF/mitogen-activated protein (MAPK) associated with proliferation (2,3). Aberrant signaling through EGFR can lead tumor-promoting cellular activities. target for cancer therapies such as gefitinib (4-quinazolinamine, N-[3-chloro-4-fluorophenylamino]-7methoxy6-[3-(4-morpholinyl) propoxy]) (4,5), which inhibits activity by reversibly competing adenosine triphosphate (ATP) at ATP-binding site within protein. Gefitinib selectively when tested against several other kinases vitro (6). In phase I trials, induced responses 10 100 unselected patients non–small-cell lung (NSCLC). Subsequently, two II radiographic regression NSCLC was observed 28% enrolled study from Japan (7) 10% Europe United States (8). On basis these studies, regulatory authorities approved treatment after chemotherapies had failed.