Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First-of-its-kind study creates new tool for targeted cancer drug development

31.10.2011
In a technical tour de force, scientists at Fox Chase Cancer Center have cataloged and cross-indexed the actions of 178 candidate drugs capable of blocking the activity of one or more of 300 enzymes, including enzymes critical for cancer and other diseases.

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).

Diana Quattrone | EurekAlert!
Further information:
http://www.fccc.edu
http://www.foxchase.org

More articles from Studies and Analyses:

nachricht Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT

nachricht Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>