Non-genetic Resistant Mechanism to EGFR Tyrosine Kinase Inhibitory Therapy

Despite initial high response rate to tyrosine kinase inhibitor (TKI) treatment, non-small cell lung cancer (NSCLC) patients whose tumors harbour activating mutation in their epidermal growth factor receptors (EGFR) gene invariably develop TKI resistance. Secondary mutation T790M in EGFR and MET amplification were found in over 50% tumors. However, there are up to 30% of cases, whose mechanisms underlying the acquired resistance remains unknown. In this study, we used whole-genome loss-of-function shRNA library screen and mRNA expression microarray to identify LAYN, EPDR1 and DNMT1 that could potentially confer TKI resistance in NSCLC cell lines. Unfortunately, knockdown of them using shRNA hairpins did not restore drug sensitivity in drug resistant models. Further studies are needed to investigate the resistance mechanism of TKI resistant NSCLC cell lines.M.Sc.2017-01-04 00:00:0