Role of nitric oxide, Src kinases in lung cancer could provide treatment answer

Such cancers require activation of the epidermal growth factor receptor, said Dr. Tony Eissa, professor of medicine – pulmonary, at BCM. Treatment with drugs that block that receptor – such as erlotinib – rapidly shrinks tumors, but often temporarily.

“This response is often followed by disease recurrence because the epidermal growth factor receptors mutate and become resistant to the drug,” he said. “Identifying more factors that prompt tumor growth will enhance treatment.”

Researchers knew that non-small cell lung cancer tissues have high levels of Src, and they found the gene for Src in the cell becomes activated when it associates with epidermal growth factor receptor. The activated Src then phosphorylates or activates by adding a phosphate molecule to other proteins that occur further along in the tumor process. One of these is inducible nitric oxide synthase, the enzyme that prompts production of nitric oxide, a cellular signaling molecule important in many systems – including the nervous, immune and skeletal systems.

“These findings imply that phosphorylation (or activation) of inducible nitric oxide synthase by Src could account for some of the Src-related roles in cancer,” said Eissa. “Our future goals are to elucidate how Src phosphorylates (or activates) inducible nitric oxide synthase and how this affects the growth of lung cancer.”

In particular, patients who become resistant to erlotinib (the drug that blocks epidermal growth factor receptor) might be helped by dasatinib, a drug that is an antibody that blocks the action of Src, he said. In addition, finding a drug that blocks the activity of inducible nitric oxide synthase might also provide benefit to patients with this disease.

Others who took part in this research include Alexey Tyryshkin, F. Murat Gorgun, Elmoataz Abdel Fattah, Tuhina Mazumdar, Lavannya Pandit and Shenyan Zeng, all of BCM. Mazumdar is now in the Texas A&M University Health Science Center School of Medicine in Houston.

Funding for this work came from The National Heart, Lung and Blood Institute.

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