Screen predicts which smoker may get lung cancer
April 7, 2010
JOSEPH HALL
Smoking kills.
But a new screening technique can predict about three-quarters of the smokers who will eventually develop lethal lung cancers, authors of a groundbreaking study say.
What’s more, the biochemical signatures captured by the diagnostic screen in most cancer-prone smokers could be blocked by a new drug that could prevent the disease from progressing, according to the study released Wednesday in the journal Science Translational Medicine.
“The idea that you can detect ... those smokers that are at highest risk to develop lung cancer, either at an early stage or before it actually occurs, is going to have an enormous, immediate impact,” says Dr. Avrum Spira, the senior study author.
The screen uses cells swabbed from a smoker’s windpipe in an outpatient “bronchoscopy” procedure that can be completed in 10 minutes.
For most people who have or are likely to develop lung cancer, the cells reveal a telltale genetic mechanism — known as the Pl3K pathway—that does not exist in smokers who will not get the lethal ailment. The genetic pathway, set in motion by something in the toxic tobacco miasma, can be detected at cancer’s earliest stage, or even before it exists.
The technique should be in clinics within the next 12 months, says Spira, a pulmonary and critical care physician at Boston Medical Centre.
“An early detection tool is really ready for prime time,” he says.
Canadian Institutes of Health Research scientist David Dankort says the diagnostic potential of the new screen could be “huge” and that the drug treatment aspect of the study was promising.
“As with all such studies, the numbers of patients analyzed will need to be increased but if this trend holds this is truly a significant finding,” says Dankort, a McGill University lung cancer expert.
“This will allow future clinicians to triage smokers at risk for therapeutic intervention with a minimally invasive procedure,” he says.
Montreal-born Spira, who trained at the University of Toronto, says about 10 to 20 per cent of smokers will develop lung cancer, which still kills more Canadians than any other form of the disease. Of those, about three-quarters show the biochemical signature — or genetic pathway — now detectable by the new screening technique.
“Lung cancer is most often diagnosed at very late stage where current therapies are largely ineffective,” Spira said. “So the idea that you can pick up the disease early, or before it even occurs, is very exciting.”
The genetic pathway picked up by the screen represents one of the earliest steps in the development of full-blown lung cancer. If the mechanism can be halted at this incipient stage, the cancer may never take hold.
Spira says an experimental drug now being tested on humans appears to do just that.
Known as myo-inositol, it appears to block the actions of the Pl3K pathway and even cure the tiny, precancerous lung lesions that bloom into tumours.
“We found that those smokers who took this drug and who had very high activation levels of this pathway…showed a response after three months in terms of the precancerous lesions getting better,” Spira says.
“That’s getting better, going away.”
Spira cautions, however, that only 10 of his study subjects have received the drug. Much more work will need to be done to assess its effectiveness.
Dankort says there are several other drugs now in clinical trials that may also prove effective at blocking the Pl3K pathway.
“While the drugs and the trials will take some time there is much promise in future therapy based on these results,” Dankort says.
Why tobacco triggers the particular genetic activity in some smokers and not others is unknown, Spira says.
“We think it probably relates to some mutation or genetic susceptibility, and we’re currently investigating that now.”
And he emphasizes that the test won’t give people who don’t have the Pl3K pathway a free pass to smoke.
First, he says, at least one-quarter of smokers who will develop lung cancer do so through another, unknown mechanism.
More important, smoking causes a host of health problems, from bronchitis to heart disease, that can kill you just as efficiently.
Researchers at Vancouver’s British Columbia Cancer Agency also contributed to the paper
