Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dual-drug therapy targets one colon cancer gene

17.08.2005


Johns Hopkins Kimmel Cancer Center scientists have found that interferon, used for 30 years to treat blood cancers, multiple sclerosis and hepatitis, selectively kills colon cancer cells when combined with another standard chemotherapy agent. New studies in cell lines suggest that the combination tactic, which targets a common gene pathway in colon cancer cells, could be more potent than either drug alone, and has fewer side effects.



"Instead of killing a tree by chopping it down, this approach focuses on cutting off the diseased branch, leaving the rest of the tree relatively unscathed," says Betsy Barnes, Ph.D., assistant professor of oncology and lead researcher.

By itself, interferon’s cell-killing activity is non-specific in targeting a variety of cells and cell-based gene activity, causing serious side effects such as heart failure and low blood counts, in addition to killing cancer cells. But in an August 15 issue of Cancer Research, the Kimmel Cancer Center scientists found one factor in interferon’s makeup that could have cancer-killing qualities, but with fewer side effects since it activates fewer genes.


Specifically, the team found that IRF5 (Interferon Regulatory Factor-5), which works as a tumor suppressor to halt cancer cell growth, is turned off by many cancers, but low levels of the suppressor protein are found in most colon cancers. That led Hopkins’ Barnes and her team to pursue its potential.

The first thing they found is that although interferon boosts IRF5 protein levels in colon cancer cells, it does not raise it enough to kill the cells. To boost IRF5 levels, the investigators combined interferon with a chemotherapy drug called irinotecan (CPT-11), a drug that damages DNA in rapidly dividing cells, rendering them unable to divide.

"We believe that interferon and irinotecan both work to increase IRF5 protein levels, but irinotecan activates the protein in the final step to initiate cancer cell death," says Barnes.

To demonstrate their theory that IRF5 is a key ingredient in the dual-drug therapy, the scientists tested various combinations of the drugs in colon cancer cell lines, with or without IRF5. Irinotecan alone causes 65 percent cell death in lines with IRF5 proteins present. Knock out IRF5 proteins and cell deaths drop to 37 percent. When the investigators combined irinotecan and interferon, more than 80 percent of colon cancer cells with IRF5 proteins died. Only 28 percent of cells died in those lines with IRF5 proteins knocked out.

"Not only does the combination of these drugs involve fewer gene activations, it may allow use of smaller amounts of both drugs and limit side effects," says Barnes. She also believes that cancer cells may find it more difficult to build resistance to two different drugs, a common problem when using single agents.

Cancers lacking tumor suppressor genes and the proteins they make are often difficult to treat because cells are unable to put the brake on abnormal growth. Her study indicates that IRF5 applies the brakes even in the absence of other tumor suppressor genes.

It is not clear whether the combination therapy would work in other cancers, since IRF5 is absent in a number of blood cancers. But since colon cancer is the third deadliest cancer in the United States, Barnes and her team will conduct further tests in genetically modified mice and potentially create a new strategy to treat the disease.

Colon cancer strikes more than 100,000 people in the United States annually and kills more than 56,000.

Funding for this research was provided by the American Cancer Society and a Flight Attendant Medical Research Institute Young Clinical Scientist Award.

Barnes’ research team on this study included Guodong Hu and Margo E. Mancl from Johns Hopkins.

Vanessa Wasta | EurekAlert!
Further information:
http://www.jhmi.edu
http://www.hopkinskimmelcancercenter.org
http://www.hopkinscoloncancercenter.org

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>