Gene Tied to Lung Cancer in Nonsmokers

Patients with mutation respond to newest drugs, study says

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HealthDay Reporter

TUESDAY, Aug. 24, 2004 (HealthDayNews) -- A genetic mutation can leave some people vulnerable to lung cancer even if they never smoked, a new study finds.

The mutation occurs in the epidermal growth factor receptor (EFGR) gene, which signals cancerous cells to divide and grow. This gene variant can appear in high concentrations in lung cancer cells, even in those of people who don't smoke.

Scientists at Memorial Sloan-Kettering Cancer Center, New York City, made this link because two new cancer drugs, Iressa and Tarceva, are both most effective against lung cancers that have the mutation, according to their report in the Aug. 23-27 issue of the Proceedings of the National Academy of Sciences.

"We think that never-smokers may have a distinct form of lung cancer compared with 90 percent of lung cancers associated with smoking," said lead author Dr. William Pao, a research fellow at the center.

"In addition, we found that tumors with mutations of EGFR are sensitive to Iressa and Tarceva, which is not found in tumors without these mutations," he added.

Both Iressa and Tarceva work by limiting the activity of EGFR, Pao said.

"Among the patients that had mutations that were sensitive to Iressa or Tarceva, three-fourths of them were never-smokers," Pao said. Never-smokers are described in this study as people who have smoked fewer than 100 cigarettes in their life.

Pao's team examined 15 tumors of patients who never smoked but had non-small cell adenocarcinoma, a common type of lung cancer. Of these, seven had mutations in their EGFR gene, the researchers found.

The team also looked at 81 tumors from former or current smokers, and found that only four had this mutation, Pao added.

In the U.S., adenocarcinomas are estimated to account for up to 50 percent of all lung cancers. While usually seen in smokers, thousands of nonsmokers also develop this type of cancer. In addition, it is the most common lung cancer in women.

Mutations in EGFR are not inherited but arise after birth, perhaps by exposure to some environmental factor, Pao explained. "But we do not know how these mutations play a role in the formation of these lung tumors," he said.

Pao's group is doing research to find out how these mutations lead to the formation of lung cancer.

"We are developing a test to identify these mutations," Pao added. "If you have these mutations, you might benefit from Iressa or Tarceva treatment earlier. At this point, we don't know how to use these drugs the best way."

These drugs work in about 10 percent of lung cancer patients, Pao noted. According to Pao, the question is whether to find patients with these mutations and treat them early with Iressa or Tarceva.

"Maybe never-smokers should be treated differently, and now we have drugs to help these patients," Pao said. "This is a step towards personalized, molecularly targeted therapy."

Dr. Len Lichtenfeld, the acting deputy chief medical officer at the American Cancer Society, called the finding significant. "Cancer treatment will ultimately be following these types of discoveries," he said.

Iressa and Tarceva are very expensive and work on only a few patients, Lichtenfeld said.

"We would like to be able to predict those patients who are more likely to respond to these drugs," Lichtenfeld said. "This research shows that we can look at the genetic makeup of these cancers and predict those who are most likely to respond."

Because Iressa and Tarceva are expensive, they are used only in the late stages of lung cancer after other treatments have failed.

Lichtenfeld noted that predicting who is likely to respond to a drug may make it more cost-effective to use these drugs early. "If you could treat patients earlier in the disease and avoid some of the more toxic chemotherapy, that would be special," he said.

More information

The American Cancer Society can tell you about lung cancer.

SOURCES: William Pao, M.D., Ph.D., research fellow, Memorial Sloan-Kettering Cancer Center, New York, Len Lichtenfeld, M.D., acting deputy chief medical officer, American Cancer Society, Atlanta; Aug. 23-27, 2004, Proceedings of the National Academy of Sciences

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