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Study reveals mechanism of lung-cancer drug resistance
Date:1/19/2012

  • The most common form of lung cancer inevitably develops resistance to the targeted drug gefitinib.
  • This study shows how this resistance develops.
  • The findings suggest a new strategy for treating non-small cell lung cancer.

COLUMBUS, Ohio New research published 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 was led by investigators with the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James). It 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 also offers a new strategy for treating non-small cell lung cancer (NSCLC), 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.

Finally, it 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.

EGFR (which stands for "epidermal growth factor receptor") is frequently overexpressed in non-small cell lung cancer (NSCLC), and this leads to uncontrolled cell proliferation. Gefitinib selectively inhibits EGFR activation and triggers cancer cells to self-destruct by apoptosis. NSCLC cells inevitably develop resistance to the drug, however. This 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 Dr. Carlo M. Croce, director of Ohio State's Human
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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

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