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Cancer drug may stymie lung disease

USC (US) — Researchers have identified a target in lung cells that may lead to new treatments for a progressive disease that ultimately robs a patient of the ability to breathe.

Characterized by scarring of the lung, idiopathic pulmonary fibrosis affects about 128,000 people in the United States, with about 48,000 new cases diagnosed annually, according to the Coalition for Pulmonary Fibrosis. Lung damage caused by the disease can’t be repaired, and treatment has focused on improving quality of life.

As reported in the Journal of Biological Chemistry, the researchers discovered that inhibiting certain proteins blocks the interaction between two cellular pathways thought to contribute to the disease.

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“There is very little research available about the mechanisms that underlie direct interactions between these cell signaling pathways, although previous studies have suggested that there is crosstalk between the two,” says Zea Borok, professor of medicine and biochemistry and molecular biology at University of Southern California and senior author of the study.

“Anti-inflammatory treatments that traditionally have been used for pulmonary fibrosis are uniformly ineffective. Our research suggests a new approach to treat a disease that is currently incurable.”

A cell signaling pathway consists of a series of signals that regulate cell behavior; studying these pathways and how information is transmitted along them may help shed light on disease origins and therapies.

Using rat lung cells, Borok and colleagues showed that the Wnt/β-catenin and transforming growth factor-β signaling pathways directly interact with one another. The interaction appears to increase expression of the α-smooth muscle actin protein, a hallmark of a biological process associated with fibrosis formation. The researchers confirmed that the interaction also occurs in human lung cells, and found that the interactions are dependent on the CREB-binding protein (CBP).

The researchers suggest using ICG-001, an experimental CBP inhibitor developed by co-author Michael Kahn, a USC provost professor in medicine and pharmacy, to stymie the pathway interaction.

They posit that ICG-001, which has been shown to be safe for clinical use in colorectal cancer patients, could be used as treatment for pulmonary fibrosis. The next step is to study its efficacy in fibrosis patients.

“Pulmonary fibrosis is the most common of the interstitial lung diseases, with a fatality rate in line with cancer,” Borok says. “These findings have the potential to provide an alternative treatment for patients afflicted by this debilitating disease.”

Researchers from the City of Hope Beckman Research Institute collaborated on the project. Beiyun Zhou, assistant professor of medicine at the Keck School, who performed most of the work during her post-doctoral training in Borok’s laboratory is first author of the study that was supported by the Hastings Foundation, Whittier Foundation, and National Institutes of Health.

More news from USC: http://uscnews.usc.edu/

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