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Cell Pathway May Be Key to Lung Cancer's Spread

Researchers express hope that finding will lead to treatments,,

FRIDAY, July 3 (HealthDay News) -- U.S. researchers say they've found a major cellular flaw that may drive the rapid spread of relapsed lung cancer.

When caught early, lung cancer can often be treated. But most cases are not detected until the disease is well advanced. Though doctors can sometimes put the cancer into remission, the disease often springs back more virulent than ever, frequently spreading to the person's brain and bones and defying most treatments.

Now, scientists at New York's Memorial Sloan-Kettering Cancer Center are focusing on the same cellular pathway that causes colorectal cancer to develop and spread. Their work appears online today in Cell.

"This is a first step in peeling back the genetic underpinnings of lung cancer metastases," said Don Nguyen, a research associate at Sloan-Kettering. "We think most patients who relapse have this pathway."

Like all biochemical pathways, the one they've pinpointed, known as WNT/TCF, is a normal part of the cell structure and allows information to pass through different molecules in a cell, including healthy ones. Problems begin when something goes wrong with the pathway, as in the case of colorectal and adenocarcinoma lung cancers.

Scientists know that an abnormal, over-stimulated WNT/TCF pathway can trigger the development of colorectal cancer. Though WNT/TCF does not appear to play a role in creating the initial adenocarcinoma, it does seem to play a decisive role in helping the tumor spread aggressively to other organs, Nguyen said.

Sendurai A. Mani, an assistant professor of molecular pathology at the University of Texas M.D. Anderson Cancer Center, said that the report "for the first time demonstrates that lung cancer acquires the molecular traits necessary to metastasize early on by activated WNT/TCF signaling."

The team of eight researchers used bioinformatics -- the highly complex computer analysis of genetic information -- to study lung tumor samples. They found that the WNT/TCF cell-signaling pathway was the only one of six pathways tested that was hyperactive in lung tumors that went on to metastasize. The pathway was normal in tumors that did not spread. They also observed that WNT/TCF hyperactivity was associated with aggressive tumors and poor survival rates.

"Lung tumors are initiated by mutations in other genes, so we were surprised that a hyperactive WNT pathway would be responsible for metastasis in lung cancer," said the study's senior author, Joan Massague, who chairs Sloan-Kettering's biology and genetics program.

Nguyen said the finding has important implications, including the possible development of therapies that target the pathway.

"There's nothing on the market yet," he said, adding that research will now focus on the weakest links of the pathway for a possible targeted treatment. "The marker can also help physicians decide whether to use more aggressive therapies, such as radiation, earlier in the treatment to help ward off any future metastasis."

Lung cancer is the nation's No. 1 cancer killer, claiming the lives of nearly 200,000 people in the United States each year. There are several forms of the disease, which is usually, but not always, caused by cigarette smoking. Adenocarcinoma forms in the glands that produce mucus and is the most common type of lung cancer in women and among people who have not smoked, according to It also spreads rapidly to distant organs, often within months, even if doctors remove the primary tumor.

Survival rates for lung cancer are poor, with only about 15 percent of people with the disease surviving five years. But the researchers hope that their study and others will speed the development of better therapies.

"Our findings suggest that using treatments that target the WNT pathway may help prevent lung cancer from repeatedly seeding itself throughout the vital organs of patients at risk for metastasis," Massague concluded.

More information

The American Cancer Society has more on lung cancer.

SOURCES: Don Nguyen, Ph.D., Memorial Sloan-Kettering Cancer Center, New York City; Joan Massague, Ph.D., chairwoman, biology and genetics program, Sloan-Kettering Cancer Center, New York City; Sendurai A. Mani, Ph.D., assistant professor, Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston July 2, 2009, Cell, online

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