Lung cancer test in the works
WASHINGTON — Scientists may have found a way to tell which smokers are at highest risk of developing lung cancer: measuring a telltale genetic change inside their windpipes.
A test based on the research is being developed in hopes of detecting this deadly cancer earlier, when it's more treatable in patients.
"They're heading toward lung cancer, and we can identify them with this genomic test," said Dr. Avrum Spira of Boston University School of Medicine, who led the research published Wednesday in the journal Science Translational Medicine.
Lung cancer — which killed nearly 160,000 Americans last year — is the leading cancer killer, and cigarette smoke is by far its main cause. Yet only a fraction of smokers develop lung cancer, and there's no way to predict who will escape it and who will not. Most people are diagnosed too late for today's treatments to do much good.
Rather than focusing on the lung itself, Spira's team took a different approach. Smoking bathes the entire respiratory tract in toxins. So he hunted for the earliest signs of impending lung cancer upstream, in how different genes are turned on and off inside the upper airway as the body tries to defend itself and those defenses weaken over time.
At least 100,000 smokers or former smokers a year have a tube snaked down their throat to look for signs of cancer if an X-ray or other test detects something suspicious, Spira explained. Bronchoscopies can be used for a look down into the lung, but Spira was interested instead in cells that line the windpipe, collected during the same procedure.
Sure enough, he found a genomic signature — a pattern of gene activity — in otherwise normal windpipes that distinguished some current or former smokers who had lung cancer from those who didn't.
Then with Dr. Andrea Bild of the University of Utah, Spira analyzed cells from 129 current and former smokers and found the genes involved were part of a well-known cancer-causing pathway named the PI3K pathway. When PI3K-related genes are too active, too much cell growth can occur, but most studies have examined those genes only in tumors.
On Wednesday, Spira reported finding PI3K activation in some current or former smokers with precancerous lesions, too, but not in those with other lung diseases.
There are some experimental drugs being designed to fight PI3K activation. One compound already had been tested in nine smokers with precancerous lesions, six of whom had their lesions improve. Spira says it's an exciting clue in the quest to develop cancer-preventing drugs.
