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“Lung cancer is the leading cause of cancer death for both men and women in the United States and more effective treatment strategies are desperately needed,” said William J. Petty, M.D., from Wake Forest. “We believe we’ve uncovered why lung cancer is currently resistant to treatment with natural and synthetic derivatives of vitamin A, drugs that are highly effective for preventing and treating other types of cancer.”
Using cell models, Petty and colleagues from Dartmouth Medical School set out to determine how resistance to this class of drugs, known as retinoids, occurs. In the process of the investigation, the researchers uncovered a protein, called RARa^1, that is critical for response to retinoid treatment.
Proteins are the products of genes and “express” the function of genes. The RARa^1 protein was detected in normal lung cells but was not expressed either in lung cancer cells studied in the laboratory or in biopsies of lung cancers from patients. By artificially expressing this protein in lung cancer cells, researchers found that sensitivity to this important class of drugs could be restored.
The research suggests that triggering RARa^1 protein expression in cancer cells could restore sensitivity to retinoid treatment. In future work, researchers plan to identify drugs that increase RARa^1 protein expression.
“Combining a retinoid with a drug that triggers expression of RARa^1 would form a new approach for treating patients with lung cancer,” said Petty, an assistant professor of hematology and oncology at Wake Forest’s School of Medicine, which is part of Wake Forest University Baptist Medical Center.