UT Southwestern researchers use drug-radiation combo to eradicate l...(rrently being tested in clinical trials ...)

"To date, no effective targeted therapy exists for NSCL cancer tumors that harbor K-RAS mutations," Dr. Scaglioni said.

Dr. Scaglioni and his team first tested the effectiveness of BEZ235 alone and found that it inhibits the proliferation of both lung cancer cells cultured in vitro and the growth of lung-cancer tumors in mice.

"The results were striking, but we wanted to find a strategy to precipitate cell death of these tumors," said Dr. Georgia Konstantinidou, a postdoctoral researcher at UT Southwestern and the lead author of the study. "We did it with radiation, which is a standard form of treatment for lung cancer."

Dr. Scaglioni's team exposed isolated cancer cells to BEZ235 followed by low doses of radiation, which induced small breaks in the DNA of the cells but otherwise would have no effect on cell survival. When this type of DNA damage occurs, cancer cells rely on the PI3K signaling pathway to survive while they repair their DNA.

"We stressed the cells in such a way that they needed this signaling pathway to survive," Dr. Scaglioni said. "Without the PI3K response, they will die."

When the researchers then treated the cells with BEZ235, which blocks PI3K, the stressed NSCL cancer cells readily underwent programmed cell death.

Dr. Scaglioni said that the next step is to use BEZ235 or similar drugs in clinical trials on NSCL cancer patients as well as other cancers, including pancreatic, colon and thyroid cancers, where the PI3K signaling pathway also plays a role.

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