Additionally, a free library of the results has been made available online to the research community. This unique library represents an important new tool for accelerating the development of an entire class of targeted cancer drugs.
The enzymes, called kinases, catalyze a wide array of vital biological activities. Unfortunately, they can also act as drivers for many forms of cancer. For this reason, the candidate drugs, called kinase inhibitors, have the potential to act as powerful anti-cancer agents. They can also interfere with normal processes in the body, however, resulting in side effects. With the new library, researchers will be able to analyze the complex interactions of these inhibitors with their targets to develop cancer drugs that block specific kinases responsible for disease while seeking to avoid major side effects. The results from the Fox Chase team's first-of-its-kind study will appear in the November issue of Nature Biotechnology.
"These results have pushed the field closer to finding truly specific inhibitors of the processes that drive cancer," says Jeffrey R. Peterson, Ph.D., associate professor in the Cancer Biology Program at Fox Chase and senior author on the new study. "We now have a collection of kinase inhibitors that are more well-characterized and understood than any other library. The next step is to use this information to identify specific, effective therapies that stop cancer in its tracks while avoiding healthy processes."
Already, some cancer patients receive kinase inhibitors to treat their disease, and many more such drugs are being developed, says Peterson. But the body contains more than 500 different kinases performing numerous functions. And the vast majority of kinase inhibitors will act on more than one kinase, and so have the potential to interfere with both cancer and the normal processes the body needs for health and survival. Not surprisingly, some of the kinase inhibitors approved for use in cancer cause significant side effects, such as cardiovascular problems.
Until the last few years, however, researchers simply didn't have the technology to observe which kinases a specific inhibitor acted upon. Recently, however, the company Reaction Biology Corporation developed a way to observe the suite of effects from one kinase inhibitor.
For the first time, Peterson and his team catalogued the activity of 178 kinase inhibitors against 300 kinases. The experiment was like observing what happens after shooting a scattergun at a wall of balloons, he says. Before, scientists could only tell if you popped one particular balloon – now, however, they can see if other balloons were hit, as well. "We're essentially shining a light on the wall of balloons so we have a much better view of the balloons that were popped."
Not surprisingly, the researchers found that kinase inhibitors targeted multiple kinases, even some that appeared to be unrelated to each other. They have deposited this massive library of results on a free website so scientists studying kinases and inhibitors can learn more about their multiple interactions.
The fact that kinase inhibitors target multiple kinases may actually be a good thing, says Peterson. Initially, scientists had hoped to find an inhibitor that targets one specific kinase involved in cancer; now, they realize that cancer rarely results from one kinase. Instead, multiple kinases likely collaborate to produce the disease -- so to stop that process, you may have to hit all of those kinases together. "It may not be possible to develop a successful drug against one kinase," he says. Indeed, some kinase inhibitors that are effective in cancer -- Sutent (sunitinib) and Sprycel (dasatinib) -- are known to target multiple kinases.
Already, the data have identified inhibitors that act on particular kinases that researchers believe are involved in cancer, but had no known inhibitor – suggesting researchers may one day be able to modify those therapies so they target only those specific kinases and others involved in cancer and avoid kinases unrelated to the disease. In addition, Peterson and his team observed the suite of various kinases affected by cancer drugs that are already in use, with the hope researchers could reduce side effects by modifying the drugs to avoid those healthy kinases.
Co-authors include Theonie Anastassiadis and Karthik Devarajan, also from the Cancer Biology Progam at Fox Chase Cancer Center, and Sean Deacon and Haiching Ma from Reaction Biology Corporation.
The study was supported by a W.W. Smith Foundation Award, the Fox Chase Cancer Center Head and Neck Cancer Keystone Program, and grants from the National Institutes of Health.
Fox Chase Cancer Center is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation's first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center's nursing program has received the Magnet status for excellence three consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For more information, visit Fox Chase's Web site at www.foxchase.org or call 1-888-FOX CHASE or (1-888-369-2427).
Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington
New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)
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...
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...
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...
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...
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)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
27.06.2017 | Power and Electrical Engineering
27.06.2017 | Information Technology
27.06.2017 | Physics and Astronomy