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Monday, December 24, 2007

Lung Cancer Cells' Survival Gene Seen as Drug Target

One of the deadliest forms of cancer appears to carry a specific weakness.

When a key gene called 14-3-3zeta is silenced, lung cancer cells can't survive on their own, researchers have found.

The gene is a potential target for selective anti-cancer drugs, says Haian Fu, professor of pharmacology, hematology & oncology at Emory University School of Medicine and Emory Winship Cancer Institute.

The research results will be published the week of Dec. 24 in the Proceedings of the National Academy of Sciences (PNAS). The paper's first author is Zenggang Li, PhD, a postdoctoral fellow in Dr. Fu's laboratory.

Lung cancer kills more Americans annually than any other type of malignancy, according to the National Cancer Institute. Yet treatment options are very limited, Dr. Fu says.

"The recent trend towards targeted therapies requires us to understand the altered signaling pathways in the cell that allow cancer to develop," he says. "If you think about genes that are dysregulated in cancer as drivers or passengers, we want to find the drivers and then, aim for these drivers during drug discovery."

Fu and his collaborator, Fadlo Khuri, MD, deputy director of clinical and translational research at Emory Winship Cancer Institute, chose to focus on the gene 14-3-3zeta because it is activated in many lung tumors. In addition, recent research elsewhere shows that survival of lung cancer patients is worse if the gene is on overdrive in their tumors, Dr. Fu says.

14-3-3 genes are found in mammals, plants and fungi. In the human body, they come in seven flavors, each given a Greek letter. Scientists describe the proteins they encode as adaptors that clamp onto other proteins. The clamping function depends on whether the target protein is phosphorylated, a chemical switch that regulates processes such as cell division, growth, or death.

"We knew that 14-3-3 is important in controlling EGFR (epidermal growth factor receptor) signaling, which is a main pathway driving lung cancer," Fu says. A couple of recently introduced drugs that were shown to be effective against lung cancer target EGFR, he adds.

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