Simultaneous inhibition of EGFR and c-Met pathways in a panel of NSCLC cell lines

22223 Background: The EGFR inhibitor, erlotinib, prolongs survival in chemotherapy-resistant NSCLC patients, although < 50% respond. Reportedly, simultaneous inhibition of EGFR (by gefitinib) and c-Met (by PHA-665752) was antiproliferative in a line selected for resistance to gefitinib alone. We hypothesized that in lines not previously exposed to either agent, simultaneous inhibition of EGFR and c-Met pathways would slow NSCLC growth more than targeting either single pathway. Methods: NSCLC lines were cultured in 96-well plates at 5000 cells/well. After 24 h, erlotinib (OSI) and the c-Met inhibitor SU11274 (Sigma) were added. Cells were recovered 3–5 d later by trypsinization and counted by hemacytometer. Receptor activation and signaling were studied in A549 by Western blotting following serum deprivation, incubation with inhibitors (3.5 h) and EGF (15 m). Results: In A549, E2 suppressed EGFR phosphorylation (pY1068), and S3 suppressed c-Met pY1230/1234/1235, confirming pathway targeting. Both drugs sup...