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A small RNA plays a big role in lung cancer drug resistance

Apr 12, 2019

APRIL 12, 2019, New York—New research led by Ludwig Harvard investigator Frank Slack and reported in the current issue of Nature Metabolism finds that a microRNA—a small fragment of non-coding genetic material that regulates gene expression—mediates drug tolerance in lung cancers with a specific mutation.

“We have identified a novel pathway required for drug tolerance that is regulated by a microRNA,” said Slack, who is also director of the HMS Initiative for RNA Medicine at the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC). “Targeting this microRNA reduces tolerance, suggesting a potential new approach for treatment of lung cancer.”

Non-small cell lung cancers—which comprise about 85% of lung cancer diagnoses—tend to be less aggressive but harder to treat than small cell lung cancers. About one in 10 of them encodes a mutated protein called EGFR, which is found on the surface of the cancer’s cells, and drugs that target this protein are in widespread use. However, many patients eventually develop resistance to these drugs. By studying drug resistant tumor cells, Slack and colleagues identified the key players driving the development of drug resistance. 

“In this study, we discovered that a microRNA known as miR-147b is a critical mediator of resistance among a subpopulation of tumor cells that adopt a tolerance strategy to defend against EGFR-based anticancer treatments,” said Slack. “We are currently testing the idea of targeting this new pathway as a therapy in clinically relevant mouse models of EGFR-mutant lung cancer.”

The BIDMC research brief from which this summary is derived can be found here.