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Drugs Target Lung Cancer in Some Non-Smokers

By Kate Ruder

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Conventional wisdom says, correctly, that people who smoke run the risk of getting lung cancer. Far less well known is the fact that a relatively small percent of lung tumors occur in people who have never smoked. Now, scientists have identified several genetic mutations that are common in the tumors of non-smokers.

Nearly 50 percent of the non-smokers in the study had the mutations, while just five percent of the smokers in the study did. (The relevant mutations were found in tumor cells only and not the rest of the body.)

The findings are all the more interesting because these genetic mutations appear to make the tumors more sensitive to the drugs Iressa and Tarceva.

“This means that a subset of lung cancers should probably be treated in a different way,” says William Pao of Memorial Sloan-Kettering Cancer Center in New York, who led the research.

In two studies published this spring, scientists reported that Iressa can have dramatic effects for lung cancer patients who have certain mutations in their tumors. The new study confirms these findings and extends them to Tarceva.

Pao and his colleagues found that seven of ten tumors that responded to Iressa had similar mutations to five of seven tumors that responded to Tarceva. The mutations, which occur in a gene called EGFR (for epidermal growth factor receptor), were present only in tumor cells and not the rest of the body.

The researchers also found that three-quarters of patients whose tumors were sensitive to either Iressa or Tarceva were non-smokers.

Drugs such as Iressa and Tarceva are part of a relatively new class of drugs that specifically targets the EGFR gene in tumors. OSI Pharmaceuticals recently applied for approval of Tarceva to the U.S. Food and Drug Administration. Astrazeneca’s Iressa has received FDA approval for late-stage treatment of lung cancers.

“This study looks not only at Iressa, but also Tarceva,” says David Johnson of Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. Johnson was not involved with the study.

“Most of us assumed that these mutations would confer susceptibility to Tarceva, but this is the first paper that really shows this,” says Johnson.

The hope is that doctors one day can begin testing for mutations in tumors to find patients, perhaps non-smokers, who are likely to benefit from drugs such as Iressa or Tarceva, but at the moment no such test is available at a doctor’s office or hospital.

For a number of years, scientists have known that certain groups of lung cancer patients are more likely to respond to Iressa—non-smokers, women, Japanese—but scientists have not known why.

“It’s been known that non-smokers have a unique form of cancer, but they’ve never been treated in a different way,” says Pao. “Now we have a molecular reason why these cancers are different and drugs to treat them.”

Daniel Haber of Massachusetts of Massachusetts General Hospital Cancer Center says: “The study is important because it presents, in print, that Iressa and Tarceva are comparable in their effects.”

“It’s also nice to see that their findings are consistent with what we know about the types of patients, for example non-smokers, whose tumors respond to the drugs,” he says.

For the purposes of the study a non-smoker is someone who has smoked fewer than 100 cigarettes in their lives.

Related Articles:
Why a Lung Cancer Drug Works so Well for Some People
DNA Mutations Help Lung Cancer Drug Work

Pao, W. et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Published online in Proceedings of the National Academy of Sciences on August 23, 2004.

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