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NCI-Funded Researchers Find Early, Measurable, and Reversible Marker of Lung Cancer Risk

Posted 04/08/2010 – Only a subset of people who actively smoke, or who smoked and quit, develop lung cancer. There is no way to identify who is at highest risk for developing the disease.  Scientists know that cigarette smoke creates a molecular field of injury throughout the respiratory tract.  In this study, published April 7, 2010 in the journal Science Translational Medicine Exit Disclaimer, scientists looked at molecular abnormalities in the lung cells of smokers at risk for lung cancer.  They found a significant increase in a genomic signature of phosphatidylinositol 3-kinase (PI3K) pathway activation in the airway cells of smokers with lung cancer and smokers with dysplastic (precancerous) lesions. This suggested that PI3K is activated before cancer development. Further, PI3K activity was decreased and precancerous changes reversed in the airways of high-risk smokers treated with the chemopreventive agent myo-inositol.  In the lab, myo -inositol was shown to inhibit the PI3K pathway. These results suggest that measuring the activity of the PI3K pathway in the airway cells of smokers is an early, measurable, and reversible event in the development of lung cancer.  By measuring these changes, a more personalized approach to lung cancer prevention or therapy may be possible. 

NCI has a phase II clinical trial of myo-inositol open to participants with bronchial dysplasia. The study site in Vancouver, B.C., is already accepting participants.  The Mayo Clinic in Rochester, Minn., and the Veterans' Affairs Medical Center in Albequerque, N.M., are scheduled to begin enrolling participants in the next several weeks.  This 6-month study will assess the value of myo-inositol in reversing precancerous changes in the lung, measure biomarkers of lung cancer and lung cancer risk, and establish a safety profile for the compound.   While myo-inositol occurs naturally in foods, studies Exit Disclaimer in people taking the compound in high quantities as a medication are limited.

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