Epidermal growth factor receptor is a receptor tyrosine kinase that is aberrantly activated in several epithelial solid tumors, and notably in NSCLC. Overexpression of the gene coding for EGFR has been found in to of NSCLC biopsies, and has been correlated with shorter survival after surgical resection, converting EGFR into an attractive therapeutic target, like erlotinib. However, only erlotinib prolonged the survival of patients with recurrent NSCLC. The deletion DEA in exon and the leucinetoarginine substitution at position. At present, it is not clear whether the TM mutation is present in a small fraction of tumor cells before treatment. Recently, it has been shown that alternative EGFRTKI inhibitors retain the ability to promote apoptosis in gefitinibresistant cancer cells. EGFR signaling is linked to multiple intracellular pathways that inhibit apoptosis and promote survival and proliferation.Apoptosis is an accurately regulated program by which vertebrates eliminate superfluous, ectopic, and damaged cells. The cell death program is at least partially suppressed during oncogenesis, thus favoring chemotherapy and radiotherapy resistance. Apoptosis can be distinguished from other cell death subroutines by means of morphologic criteria, including chromatin condensation. Cells that succumb to apoptosis eventually break down into membraneenclosed bodies, which, in vivo, are XY1 engulfed by resident phagocytic cells and usually fail to elicit inflammatoryimmune responses. Apoptosis may be executed via the extrinsic pathway, which along the death receptors deathinducing signaling complex emanates from the extracellular environment and is propagated caspase axis, or through an intracellular cascade of events that involves mitochondria. After mitochondrial membrane permeabilization, cytotoxic proteins that normally reside in the intermembrane space are liberated into the cytosol, and can either favor directly the activation of the caspases, as does cytochromec, as do apoptosisinducing factor. In addition, we describe the mechanisms through which BMS exerts is cytostatic and cytotoxic effects.Thereafter, cells were harvested, lysed for the extraction of RNA, and processed to analyze gene expression, as previously reported. For proliferation assays, to cells were seeded in well plates hbefore the treatment with BMS or erlotinib. In both cases, treatments lasted a total of h, after which plates were analyzed for cell proliferation.mL of the same medium and allowed to stand at room temperature for min.The resulting cell suspension was seeded into a well plate. Transfected cells were cultured for hbefore the administration of BMS. Finally, plates were analyzed for cell proliferation.For FACS analysis, H cells were reverse transfected after a slightly Flunisolide modified protocol.BMS is a novel specific inhibitor of EGFR, exhibiting an in vitro IC of f nmolL.At higher concentrations, it acts also on other members of the EGFR family as well as on VEGFR. BMS inhibits the proliferation of NSCLC cell lines, showing a marked effect on the H cell line that expresses an EGFR mutation that is associated with clinical resistance against erlotinib.It was associated with a marked increase in cells manifesting signs of apoptosis including the dissipation of the mitochondrial transmembrane potential and the permeabilization of the plasma membrane were by far more sensitive to BMS than H NSCLC cell lines. Transmission electron microscopy revealed that H cells transit from a normal morphology to fullblown apoptosis when treated with BMS.