UT Southwestern researchers use drug-radiation combo to eradicate l...( DALLAS Oct. 29 2009 Researchers at...)

DALLAS Oct. 29, 2009 Researchers at UT Southwestern Medical Center have eliminated non-small cell lung (NSCL) cancer in mice by using an investigative drug called BEZ235 in combination with low-dose radiation.

In a study appearing in the October issue of Cancer Research, UT Southwestern researchers found that if they administered BEZ235 before they damaged the DNA of tumor cells with otherwise nontoxic radiation, the drug blocked the pro-survival actions of a protein called PI3K, which normally springs into action to keep tumor cells alive while they repair DNA damage.

Researchers tested this novel therapeutic strategy in mice transplanted with NSCL cancers obtained from patients.

They found that tumors in the mice treated with BEZ235 alone were significantly smaller than those in mice not given the drug. Although the tumors stopped growing, they did not die.

By contrast, tumors were completely eradicated in mice treated with a combination of BEZ235 and radiation.

"These early results suggest that the drug-radiation combination might be an effective therapy in lung cancer patients," said Dr. Pier Paolo Scaglioni, assistant professor of internal medicine at UT Southwestern and senior author of the study.

NSCL cancer is a leading cause of cancer-related deaths worldwide. The cancer cells often harbor mutations in a gene called K-RAS. Patients with such K-RAS mutations typically are more resistant to treatment with radiation and have a poor prognosis.

K-RAS mutations lead to the activation of networks, or pathways, of several so-called signaling proteins, which in turn play key roles in the regulation of tumor growth. One of these proteins, called PI3K, is activated to keep cells alive that have sustained DNA damage.

Several components of the signaling pathways, including PI3K, have been investigated as possible anti-cancer drug targets. The investigational drug BEZ235 is cu
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