Navigation Links
UT Southwestern researchers use drug-radiation combo to eradicate lung cancer
Date:10/29/2009

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 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," 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.


'/>"/>

Contact: Connie Piloto
Connie.piloto@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

Related biology news :

1. UT Southwestern patient first in North Texas to receive newest-generation heart failure device
2. Ice cream may target the brain before your hips, UT Southwestern study suggests
3. UT Southwestern researchers examine mechanisms that help cancer cells proliferate
4. UT Southwestern researchers probe kidney damage, protection in lupus
5. Diabetics on high-fiber diets might need extra calcium, report UT Southwestern researchers
6. Two UT Southwestern researchers awarded Sloan fellowships
7. UT Southwestern researchers identify molecule that helps the sleep-deprived to mentally rebound
8. UT Southwestern researchers disrupt biochemical system involved in cancer, degenerative disease
9. Natural brain substance blocks weight gain in mice, UT Southwestern researchers discover
10. UT Southwestern scientist honored among best in Texas research
11. UT Southwestern researchers identify gene linked to inherited form of fatal lung disease
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UT Southwestern researchers use drug-radiation combo to eradicate lung cancer
(Date:2/4/2016)... LONDON , Feb. 4, 2016 ... is apparently one of the most popular hubs ... Project, MetaHIT and other huge studies of human ... that past few years, the microbiome space has ... applied biomedical research. This report focuses on ...
(Date:2/3/2016)... Feb. 3, 2016 ... of the "Emotion Detection and Recognition ... and Others), Software Tools (Facial Expression, Voice ... Users,and Regions - Global forecast to 2020" ... --> http://www.researchandmarkets.com/research/d8zjcd/emotion_detection ) has announced the ...
(Date:2/2/2016)... 2016 Technology Enhancements Accelerate Growth of X-ray Imaging ... digital and computed radiography markets in Thailand ... Indonesia (TIM). It provides an in-depth ... well as regional market drivers and restraints. The study ... and market attractiveness, both for digital and computed radiography. ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... 11, 2016   BioInformant announces the February ... Research Products, Opportunities, Tools, and Technologies – Market Size, ... The first and ... cell industry, BioInformant has more than a decade of ... market, by stem cell type. This powerful 175 page ...
(Date:2/10/2016)... WASHINGTON , February 10, 2016 Early-career ... , Peru , Uganda ... their life-enhancing work in health and nutrition   Indonesia ... Uganda and Yemen are ... sciences and epidemiology. They are also celebrated for mentoring young women scientists ...
(Date:2/10/2016)... Feb. 10, 2016  IsoRay, Inc. (NYSE MKT: ISR), ... and medical radioisotope applications for the treatment of prostate, ... announced its financial results for the second quarter and ... 2015. --> --> ... of fiscal 2016, which ended December 31, 2015, a ...
(Date:2/10/2016)... ... February 10, 2016 , ... LATHAM, NEW YORK... ... SPIE Photonics West conference in San Francisco’s Moscone Center from February 16-18, ... same venue. , These latest InGaAs PIN diode standard packages feature a TO-46 ...
Breaking Biology Technology: