In Clinical Cancer Research this week, researchers in Austria and Hungary report their genome-wide microRNA expression profiling of non-small-cell lung cancer. The team analyzed the expression of 856 miRNAs in non-small-cell lung cancer A549 cells both before and after treatment with a DNA methyltransferase inhibitor alone and in combination with a histone deacetylase inhibitor. "By comparing microarray data of untreated and drug-treated A549 cells, we identified 33 miRNAs whose expression was upregulated after drug treatment and which are associated with a CpG island," the authors write. "Thirty of these miRNAs were found to be methylated in at least 1 of 11 NSCLC cell lines analyzed. Moreover, miR-9-3 and miR-193a were found to be tumor specifically methylated in patients with NSCLC." This suggests that methylation is an important mechanism in the inactivation of certain miRNAs in lung cancer, they add.
Also in Clinical Cancer Research this week, researchers in New York and Massachusetts describe a new family of sensitizing EGFR mutations in lung adenocarcinoma. The team studied lung cancer patients with EGFR exon 19 insertions, and found that patients with these insertions were predominately female and never-smokers. "EGFR exon 19 insertions are a newly appreciated family of EGFR-TKI–sensitizing mutations, and patients with tumors harboring these mutations should be treated with EGFR-TKI," the authors write. "While these mutations may be missed through the use of some mutation-specific assays, the addition of PCR product size analysis to multigene assays allows sensitive detection of both exon 19 insertion and deletion mutations."
Finally in Clinical Cancer Research this week, researchers in the US and UK explore combined MEK and VEGFR inhibition in an orthotopic model of human lung cancer. The team injected NCI-H441 or NCI-H460 KRAS-mutant human non-small-cell lung cancer cells into mice, and then treated them with selumetinib, cediranib, paclitaxel, or selumetinib plus cediranib. When control mice began dying, the team assessed the mice in the other groups, and found that selumetinib and cediranib inhibited lung tumor growth and reduced locoregional metastasis. In addition, the team found that the two drugs in combination "markedly enhanced their antitumor effects, with near complete suppression of metastasis." This, the team adds, suggests that "combining selumetinib and cediranib represents a promising strategy for the treatment of NSCLC."