Scientists from UT Southwestern Medical Center have suggested a novel therapeutic strategy that would completely eradicate lung cancer.
Researchers Pier Paolo Scaglioni and Georgia Konstantinidou have shown that using an investigative drug called BEZ235 in combination with low-dose radiation successfully eliminated non-small cell lung (NSCL) cancer in mice.
"These early results suggest that the drug-radiation combination might be an effective therapy in lung cancer patients," said Dr. Scaglioni.
NSCL 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 currently being tested in clinical trials against PI3K and another signaling protein called mTOR.
To date, no effective targeted therapy exists for NSCL cancer tumors that harbor K-RAS mutations," said Scaglioni.
During the study, researchers 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. Without the PI3K response, they will die," said Scaglioni.
When the researchers treated the cells with BEZ235, which blocks PI3K, the stressed NSCL cancer cells readily underwent programmed cell death.