Gene expression signature in the upper
airway
of smokers predicts lung cancer
Avrum Spira, MD
Boston University's Avrum Spira, MD, discusses the discovery of a gene expression signature and a potential preventative treatment for lung cancer
A group of scientists, led by Dr. Avrum Spira, has used Affymetrix expression arrays to discover an 80-gene biomarker that can identify lung cancer in its early stages. Their research has shown that the gene expression signature of lung cancer can be detected not only in deep lung tissues, but also in the cells that line the upper airway. This discovery may lead to less invasive clinical procedures that can be used to diagnose lung cancer, the number one cause of cancer death worldwide.
Read more >The Affymetrix platform is not only an excellent platform for research and discovery, but we think it can ultimately be used for clinical applications.
In 2007, Dr. Spira collaborated with a team of scientists to look at epithelial cells obtained from bronchoscopies of the upper airways of smokers suspected to have lung cancer. Using GeneChip® Human Genome U133A Arrays, they discovered a gene expression signature that can accurately distinguish smokers who had lung cancer from smokers with benign diseases of the lung. They found that the gene expression profile of the cytologically normal epithelial cells found in the windpipe could be used as a sensitive and specific lung cancer biomarker. Their hope is to develop a clinical test that can be used to detect lung cancer in its early, curable stages.
In a follow-up study, Spira and his colleagues focused on pathways specifically related to cancer. They reanalyzed data from their earlier study and found that genes associated with the PI3-kinase (PI3K) pathway were differentially activated in the airways of smokers with lung cancer. The PI3K pathway was previously identified as an important pathway in several other cancers due to its role in regulating proliferation and survival of cells.
Recently, the team of researchers studied the effects of myoinositol, a naturally occurring compound known to inhibit the PI3K pathway, on the development of lung cancer. They found that the drug not only decreased the activity of PI3K in the affected cells, but also healed the precancerous lesions in a significant subset of individuals who received treatment. The results of this pilot study reveal the potential for myo-inositol to be used as a treatment for lung cancer and other cancers that may be caused by changes in PI3K activity.
"So far, we've demonstrated that PI3K activity can be reversed by myo-inositol and that may associate with reduction of disease risk," says Spira. "In the future we need to do a much larger study over a longer period of time to be certain that this is true in lung cancer and perhaps other cancers as well."
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