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Lung Cancer in Nonsmokers Tied to Mutation

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Although lung cancer is predominantly a disease of smokers, about 10 percent of those suffering from it have no history of tobacco use. New research indicates that a distinct gene mutation is common in lung cancers of these so-called "never smokers" who have smoked fewer than 100 cigarettes in their lifetimes.

William Pao of Memorial Sloan-Kettering Cancer Center and his colleagues performed DNA testing on lung cancer tumors from patients given one of two drugs, gefitinib or erlotinib (brand names Iressa and Tarceva). The researchers found that 81 percent of those who had responded favorably to treatment had tumors with mutations in the gene for epidermal growth factor receptor (EGFR), an enzyme that helps trigger DNA replication and cell division. Mutations in the EGFR gene have previously been implicated in other cancers and the results, published in this week's online edition of the Proceedings of the National Academy of Sciences, confirm that gefitinib and erlotinib inhibit the activity of EGFR. "Lung cancers that respond to these drugs appear to be, for lack of a better word, addicted to EGFR," Pao says. Drugs that block EGFR are thus able to shrink tumors with this "Achilles' heel."

Patients in the study who responded well to the drugs included a large fraction of never smokers. To investigate this apparent correlation, the scientists tested an additional 96 tumors from patients who had yet to receive treatment. Out of 15 never smokers in this sample, seven exhibited the EGFR mutation in their tumors, whereas only four out of 81 smokers did. Pao stressed that these mutations are not found in the patients' normal tissues, so "one can't pass them on to one's children." Instead, people apparently acquire the mutation at some point in their lives.

Side effects from gefitinib and erlotinib are relatively minor compared to traditional cancer treatments. The drugs are usually given to patients that have already been through surgery and/or chemotherapy. Pao thinks that in the future, treatments will be tailored so that those who test positive for certain mutations can start on drugs that target the relevant biological pathways. Unfortunately, as of now, EGFR inhibitors are only effective for a limited time, as tumors eventually build up a resistance to the drugs.

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