From: Reuters
Published March 12, 2008 08:40 PM

Study shows way to predict lung cancer recurrence

By Maggie Fox, Health and Science Editor

WASHINGTON (Reuters) - It may be possible to predict whose lung cancer is likely to come back after surgery has apparently cured it, U.S. researchers reported on Wednesday.

And the findings could lead to more effective treatments for lung cancer, a theory they are testing, the researchers reported in the New England Journal of Medicine.

They saw clear changes in four genes in patients whose cancer came back within five years after surgery and said the findings might be used as the basis for a test.

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Patients found to have a high risk might consider special chemotherapy after surgery.

"These people are at increased risk of recurrence. We think that there are numerous ways that you can take care of them," said Dr. Malcolm Brock of Johns Hopkins University in Baltimore, who led the study.

"One is of course more chemotherapy. But we also believe that by giving them targeted therapies, new types of therapies, we can help these patients," Brock said in a telephone interview.

Brock's team tested 157 patients with stage I non small cell lung cancer who had had small tumors surgically removed.

Of the patients, 51 had the cancer come back within 40 months -- just over three years -- while 116 stayed tumor-free.

The researchers found changes called methylation of the promoter region in four genes among the patients whose cancer returned. Methylation is a process that switches genes on and off.

"The four genes of interest in our study are p16, CDH13, APC, and RASSF1A. They are involved in cell-cycle control (p16), invasion and metastasis (CDH13, APC), and Ras signaling (RASSF1A)," the researchers wrote.

The researchers' test has been licensed to Belgian biotech company OncoMethylome.

'DNA FORENSICS'

"This is DNA forensics for cancer," Brock said.

"All of these tumors that we are talking about are early stage tumors. They are very small," he added. Yet a third of patients with such tumors have their cancer return.

After surgery, it appears all the cancer is gone. Pathologists look at the nearby tissue and lymph nodes under a microscope and declare the patient cancer-free.

"But in 40 months the patient comes back with metastatic disease in all of their body. How is that possible?" Brock asked. "It must be that the microscope, which is a 17th century innovation ... is not picking up all of the disease."

But the DNA test does, Brock believes. And the findings could lead to new treatments for lung cancer, one of the deadliest cancers.

Some drugs can home in on these changes however -- notably drugs used to treat myelodysplastic syndromes, sometimes known as pre-leukemia. They are known as hypomethylating agents and include 5-azacytidine, decitabine and lenalidomide.

Brock's team is also testing these agents in lung cancer patients. "There are lots of them and there are lots of choices," he said.

He believes the test has wider uses. "We really think that if this can be validated that it would have broader applications to other solid tumors," he said.

"It gives weight to an idea that your tumor DNA and my tumor DNA might be slightly different. It might even show us ways that we can do personalized therapy."

Lung cancer kills more than 1 million people each year worldwide. Only 15 percent of patients survive five years or more.

(Editing by Mohammad Zargham)

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