An evaluation of molecular changes in non-small cell lung cancer (NSCLC) cell lines with acquired resistance to NVP-BEZ235, a novel P13K/mTOR dual inhibitor

[Truncated abstract] PI3K/mTOR inhibitors are currently being evaluated extensively in many cancers, including lung cancer. However, as with other cancer therapy, it is likely that acquired resistance will be a major contributing factor in treatment failure. Resistance mechanisms to PI3K/mTOR inhibitors are not well characterized. This study aimed to generate and elucidate mechanisms of acquired resistance to BEZ235, a PI3K/mTOR inhibitor, in lung cancer cells. Acquired resistance was generated by continual exposure of cells to parental IC50 concentrations of BEZ235, followed by monoclonal selection. Protein levels, cell migration, and cell cycle analysis were evaluated using standard techniques. Deep RNA sequencing (RNA-seq) and Reverse phase protein array analysis (RPPA) was used to identify possible resistance mediators...