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Blood, Spit, and Breath: Scientists Search for Noninvasive Tests for Lung Cancer
Cancer has a way of hunkering down inconspicuously and slowly taking over organs. Lung cancer, especially, often goes unnoticed until patients get tired of wheezing or coughing and go see their doctor. While efforts to study imaging continue (see story, p. 190), other researchers are focusing on finding signs of lung cancer in blood, sputum, and even breath. They hope to use these markers to find the cancer early and predict how aggressive it will be.
According to Li Zhong, Ph.D., now at the City of Hope in Duarte, Calif., about 25% of early-stage lung cancers show up with imaging technologies, and some cancer biologists think that a marker in an easily extracted bodily fluid could help find the lost majority.
"So far we don't have a biomarker for lung cancer. It's a pity because most lung cancer goes undiagnosed," says Pierre Massion, M.D., a pulmonologist at Vanderbilt Ingram Cancer Center in Nashville, Tenn.
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Zhong and his colleagues are using cancer-associated proteins as the bait to fish for antibody markers in blood. Because cancer cells produce proteins that are not normally found in healthy people, their immune systems make antibodies to them. Zhong's team used a collection of more than 200 of these abnormal proteins from lung cancer cells and mixed them with blood from patients or healthy donors. Some of the cancer patients had antibodies that recognized proteins that healthy people did not have. Eventually, the researchers narrowed the 200 proteins to five that were most often found in cancer cells and least often in normal cells. Then they tested 40 blood samples that had been drawn 1–5 years before the donors were diagnosed with cancer. They identified as cancerous 32 of the 40 samples that would eventually become malignant.
Massion hasn't been as lucky looking for proteins from lung cancer cells directly in the blood. Blood is chock full of proteins, 95% of which are from a small subset. But the other 5% represent a vast sampling of the remaining proteins that human bodies make. "We have figured out that the serum is extremely complex," he says. To help narrow down the proteins to those from cancer cells, his team is screening tumors for collections of proteins that lung cancers produce. "We're going back to tissue and trying to find candidate markers from tissue first," he says.
Other researchers agree that blood will be a difficult choice for early lung cancer detection diagnostics. "Anything that's going on in the body [could] show up in the blood," says Steven Belinsky, director of the lung cancer program at the Lovelace Respiratory Research Institute in Albuquerque, N.M. Having worked with blood in the past, he is now turning his attention to sputum, the thick secretions that people cough up from their lungs. "With sputum, you know exactly where it came from," he says.
Belinsky and his colleagues at Johns Hopkins University in Baltimore pull DNA from the sputum and look for particular modifications on it called methyl groups. As cancers grow and develop, some of their genes get tagged with methyl groups, inhibiting the gene's ability to function. His gene of interest, ASC/TMS1, appears to become methylated in late-stage cancers, and his group showed in 2006 that they can detect the added methyl groups in sputum in the same percentages that they are detected in cancer samples.
All of these researchers agree that these methods are early in development for lung cancer prediction, so they are hunkering down with their markers, hoping to find an effective way to identify the deadly disease. Then comes the difficult task of determining in large controlled trials whether these markers would actually help people.
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J Natl Cancer Inst 2007 99: 190-195.
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