This month’s featured article is from the lab of John T-A Hsu of National Chiao Tung University in Hsinchu, Taiwan. The article regarding research on lung cancer cells was published 19 May 2016 in the journal OncoTargets and Therapy.
This study investigates how non-small cell lung cancers (NSCLC) develop resistance to therapies that target epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). These EGFR TKI therapeutics are the most common first-line treatments, but all patients eventually develop resistance to the drugs. Therefore, studies aimed at mechanisms of EGFR TKI resistance are necessary for developing more potent therapeutics. In this study, the authors looked at the immediate response of NSCLC’s to EGFR TKI treatment with an eye towards how these responses lead to drug resistance.
Working with cultured NSCLC cell lines, the authors showed that treatment with gefitinib quickly modified the morphology of the cells over a time course of 72 hours. They then used Phalanx Biotech’s Human OneArray Whole Genome Microarray to investigate the differentially expressed genes underlying these changes in morphology and cell adhesion. Lists of differentially expressed genes were subjected to Gene Set Enrichment Analysis and KEGG Pathway Visualization (these analyses are included in our standard OneArray Microarray Service package – read more HERE and HERE). The microarray results clearly pointed to adhesion-related pathways being affected by EGFR TKI treatment.
Next, the authors validated the microarray results by focusing on a group of genes for qPCR. These genes are involved in the core components of cell adhesion pathways. The qPCR results were consistent with the microarray data, and the authors further looked at these genes at earlier and shorter time scales than the microarray data. They also looked at the protein expression results for this small group of targets.
Overall, this study clearly demonstrates that NSCLCs can survive following EGFR TKI drug treatment by modifying cell adhesion pathways. Given these results, the authors propose future therapies that target both EGFR signaling and adhesion-related pathways.
Reference
Wang H-Y et al. Non-small-cell lung cancer cells combat epidermal growth factor receptor tyrosine kinase inhibition through immediate adhesion-related responses (2016). OncoTargets and Therapy 9: 2961-2973.