U.S. study reveals mechanism of lung cancer drug resistance

New research published this week in Nature Medicine indicates that targeted drugs such as gefitinib might more effectively treat non-small cell lung cancer if they could be combined with agents that block certain microRNAs. The study, led by investigators with the Ohio State University Comprehensive Cancer Center, shows that overexpression of two genes called MET and EGFR causes the deregulation of six microRNAs, and that this deregulation leads to gefitinib resistance. The findings support the development of agents that restore the levels of these microRNAs. It offers a new strategy for treating non-small cell lung cancer, which is responsible for about 85 percent of the 221,000 lung-cancer cases and 157,000 deaths that occur annually in the United States. It also suggests that measuring the expression levels of certain microRNAs -- those controlled by the MET gene -- might predict which lung-cancer cases are likely to be resistant to gefitinib. Epidermal growth factor receptor (EGFR) is frequently overexpressed in non-small cell lung cancer, and this leads to uncontrolled cell proliferation. Gefitinib selectively inhibits EGFR activation and triggers cancer cells to self-destruct by apoptosis. However, non-small cell lung cancer cells inevitably develop resistance to the drug. The study reveals how this resistance occurs. "Our findings suggest that gefitinib resistance that is caused by MET overexpression is at least partly due to miRNA deregulation, " says principal investigator Carlo Croce.