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Researchers Uncover Clues to Vitamin A Resistance in Lung Cancer

WINSTON-SALEM, N.C. -- Researchers hope that a newly identified protein can one day help improve treatment for lung cancer. The findings are reported today by researchers from Wake Forest University School of Medicine and Dartmouth Medical School in the “Journal of the National Cancer Institute.”

“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 W. Jeffrey 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 RARß1’, that is critical for response to retinoid treatment. Proteins are the products of genes and “express” the function of genes. The RARß1’ 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 RARß1’ protein expression in cancer cells could restore sensitivity to retinoid treatment. In future work, researchers plan to identify drugs that increase RARß1’ protein expression.

“Combining a retinoid with a drug that triggers expression of RARß1’ would form a new approach for treating patients with lung cancer,” said Petty, formerly at Dartmouth Medical School and currently an assistant professor of hematology and oncology at Wake Forest’s School of Medicine, which is part of Wake Forest University Baptist Medical Center.

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Citation:
• Petty WJ, Li N, Biddle A, Bounds R, Nitkin C, Ma Y, et al. A Novel Retinoic Acid Receptor Beta Isoform and Retinoid Resistance in Lung Carcinogenesis. J Natl Cancer Inst 2005;97:TKTK.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

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Contact: Jonnie Rohrer, jrohrer@wfubmc.edu, 336-716-6972; Shannon Koontz, shkoontz@wfubmc.edu, or Karen Richardson, krchrdsn@wfubmc.edu, at (336) 716-4587.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 30th in primary care, 41st in research and 14th in geriatrics training among the nation's medical schools. It ranks 32nd in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.

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