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).
Graphene gives a tremendous boost to future terahertz cameras
16.04.2019 | ICFO-The Institute of Photonic Sciences
Mount Kilimanjaro: Ecosystems in Global Change
28.03.2019 | Julius-Maximilians-Universität Würzburg
Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.
Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...
A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter
A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.
Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...
The technology could revolutionize how information travels through data centers and artificial intelligence networks
Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...
Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.
Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...
17.04.2019 | Event News
15.04.2019 | Event News
09.04.2019 | Event News
23.04.2019 | Information Technology
23.04.2019 | Earth Sciences
23.04.2019 | Life Sciences