Natural Health

Tests to Help Avoid Recurrence of Lung Cancer

By: Neomi Heroux
Published: Tuesday, 25 March 2008
Xray of lungs

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In the very near future it may be possible to prevent the recurrence of lung cancer in patients who have been treated for the disease.

Researchers at Johns Hopkins Kimmel Cancer Center have discovered clearly recognizable genetic alterations in tumors and tissue removed from patients with early-stage lung cancers. The alterations in genes look like good predictors of which cancers are more likely to occur.

Malcolm Brock, M.D., associate professor of surgery at Johns Hopkins says “This is DNA forensics for cancer. While there may be no trace of cancer that we can spot after surgery with a microscope, the DNA evidence from these tumors may have been left at the scene, especially in lymph nodes.”

The discovery could change the approach to treating even the smallest lung cancers – the size of a pea – which recur within five years in 30 to 40 per cent of patients. The particular molecular flags which were identified are chemicals known as methyl groups. These chemicals latch on to the DNA ladder structure of a gene. Methylation is commonly recognized in association with the formation and development of cancers because they serve as signals to cells to switch certain genes on or off. Disruption of these signals may cause a cascade of abnormal proteins that lead to cancer or its recurrence.

In a study published in the March 13 issue of the New England Journal of Medicine, Brock and his team report they combed through more than 700 surgical samples from 167 early stage, non-small cell, lung cancer patients searching for specific methylation patterns linked to the disease.

Tumor and lymph node tissue from 51 patients whose cancer recurred within 40 months, were compared with samples from the remaining 116 patients whose cancers did not recur.

All of the samples were tested for methylation on seven genes linked to the development of lung cancer. Four of those – p16, H-cadherin, APC, and RASSF1A - showed the highest amounts of methylation in patients whose cancers recurred. For many of the genes there was a twofold difference in methyl marks between recurrent cancers and those that did not return.

“The DNA evidence we see for many of the recurring cases suggests it may be wise, if our work is confirmed, to reclassify such cancers as advanced disease instead of early stage.” Says Brock

The cancer returned more quickly in patients with higher than normal methylation in two genes known as p16 and H-cadherin. In some instances the recurrence was within a year.

According to Kimmel Cancer Center medical oncologist James Herman, M.D., if these results are confirmed it may lead doctors to consider treating high risk patients more aggressively with chemotherapy after surgery. He also believes that therapies which target these gene patterns, by stripping off methyl groups, hold promise as well. “These marks of aggressive disease also are themselves targets for therapy,” said Herman.

Additional studies are being conducted on the methyl markers on patients currently being treated at Johns Hopkins. Brock believes the tests also have 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 the way that we can do personalized therapy.”

Lung cancer is the second most common cancer in the United States and the most deadly. Cure rates for lung cancer are far lower than other common cancers such as breast or prostate. According to the National Cancer Institute there will be approximately 215,000 new cases of lung cancer in 2008 and 161,800 deaths from the disease. Only 15 percent of patients survive five years or more.