Furthermore, the molecule was equally high in early stage tumors and late stage tumors, suggesting that this change happens early in lung cancer development, says Croce, who also directs Ohio State's Human Cancer Genetics program.

Using lung cancer cell lines, the investigators learned that EGFR regulates miR-21. For example, altering EGFR levels caused corresponding changes in miR-21.

Last, the investigators took cells that had a mutated EGFR gene and treated them with an anti-EGFR agent (the agent was related to gefitinib and erlotinib, targeted drugs used to treat lung cancers with EGFR mutations). As expected, many of the cells died. But when they blocked both EGFR and miR-21, the proportion of cells killed rose still more.

Overall, Croce says, "Our study suggests that the combined use of an EGFR inhibitor and a miR-21 inhibitor might improve therapy for many cases of lung cancer, and rescue lung cancer cases that have acquired resistance to several targeted drugs."

Funding from the Intramural Research Program of the National Institutes of Health, National Cancer Institute and Center for Cancer Research supported this study.

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