Ohio State University Comprehensive Cancer Center and at the National Cancer Institute scientists have identified a protein that appears to play a vital role in lung cancer in non-smokers.
They hope that the new discovery could lead to improved therapy for lung cancer in both never-smokers and smokers, including those with tumors resistant to targeted drugs such as gefitinib.
While examining lung tumors from people who had never smoked, the researchers found high levels of a molecule called MIR-21.
"Several important lung cancer drugs target EGFR mutations, but these agents are ineffective in about 30 percent of cases in which the mutation is present," said co-principal investigator Dr. Carlo M. Croce, professor of Molecular Virology, Immunology and Medical Genetics at the Ohio State University Comprehensive Cancer Center, James Cancer Hospital And Solove Research Institute.
"Our study suggests that developing agents to inhibit MIR-21 might improve these anti-EGFR therapies," he added.
Core and his colleagues began their study by comparing 28 cases of lung tumor tissue and nearby healthy lung tissue from never-smokers for changes in microrna, molecules that help cells regulate the kind and amount of proteins they make.
The cancer cells showed abnormally elevated levels of five micrornas, with MIR-21 increased two and a third times, the highest of all.
Furthermore, the molecule was equally high in early stage tumors and late stage tumors, suggesting that this change happens early in lung cancer development, said Croce.
Using lung cancer cell lines, the investigators learned that EGFR regulates MIR-21. For example, altering EGFR levels caused corresponding changes in MIR-21.
For further research, 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."
The study appears in Proceedings Of The National Academy Of Sciences.