Deregulation of a Network of mRNA and miRNA Genes Reveals That CK2 and MEK Inhibitors May Synergize to Induce Apoptosis KRAS-Active NSCLC:

KRAS-activation mutations occur in 25% to 40% of lung adenocarcinomas and are a known mechanism of epidermal growth factor receptor inhibitor (EGFRI) resistance. There are currently no targeted therapies approved specifically for the treatment of KRAS-active non–small cell lung cancers (NSCLC). Attempts to target mutant KRAS have failed in clinical studies leaving no targeted therapy option for these patients. To circumvent targeting KRAS directly, we hypothesized that targeting proteins connected to KRAS function rather than targeting KRAS directly could induce cell death in KRAS-active NSCLC cells. To identify potential targets, we leveraged 2 gene expression data sets derived from NSCLC cell lines either resistant and sensitive to EGFRI treatment. Using a Feasible Solutions Algorithm, we identified genes with deregulated expression in KRAS-active cell lines and used STRING as a source for known protein-protein interactions. This process generated a network of 385 deregulated proteins including KRAS and...