The cause of lung cancer in never-smokers is poorly understood, but a study led by investigators at the Ohio State University Comprehensive Cancer Center and at the National Cancer Institute has identified a molecule believed to play an early and important role in its development.
The findings, published online recently in the Proceedings of the National Academy of Sciences, may lead to improved therapy for lung cancer in both never-smokers and smokers, including those with tumors resistant to targeted drugs such as gefitinib.
The study examined lung tumors from people who had never smoked and found high levels of a molecule called miR-21. The levels were even higher in tumors that had mutations in a gene called EGFR, a common feature of lung cancer in never-smokers.
"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," says 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."
About 15 percent of the 219,000 lung cancer cases expected this year in the United States – 32,850 people – will occur in individuals who have never smoked.
Croce 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. An earlier study of smoking-related lung cancer by the same investigators also showed elevated levels of that molecule.