Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers create drug to keep tumor growth switched off

12.02.2010
A novel – and rapid – anti-cancer drug development strategy has resulted in a new drug that stops kidney and pancreatic tumors from growing in mice. Researchers at the Moores Cancer Center at the University of California, San Diego, have found a drug that binds to a molecular "switch" found in cancer cells and cancer-associated blood vessels to keep it in the "off" position.

"We locked the kinase switch in the off position in cancer and in tumor-associated blood vessels," which differs from the way current inhibitors attempt to block active kinases, said David Cheresh, PhD, professor and vice chair of pathology at the UCSD School of Medicine and the Moores UCSD Cancer Center, who led the work.

The new approach employs scaffold-based chemistry combined with supercomputer technology, allowing for rapid screening and development of drugs that are more selective for the tumor. The development and screening processes were used to identify potential drug candidates able to halt a growth signaling enzyme, or kinase, which can foster tumor blood vessel and tumor growth. According to the researchers, the novel approach may become a useful strategy in cancer drug development. The study appears online the week of February 8, 2010, in the Proceedings of the National Academy of Sciences.

In this "rational design approach," Cheresh and his co-workers used the supercomputer at the San Diego Supercomputer Center to custom-design molecules that stabilized the inactive forms of two similar kinases, PDGFRâ and B-RAF – both of which are found to be activated in tumors and in blood vessels that feed tumors. Since PDGFRâ and B-RAF work cooperatively, keeping both turned off causes synergistic effects in tumors, according to Cheresh.

"We custom design a drug for a target that we know either plays a role in blood vessel angiogenesis or tumor invasion," said Cheresh. "By doing this on the computer screen and effectively locking the target in the off position, we can generate selective drugs that are expected to produce minimal side effects. Working with a series of chemical scaffolds, we are able to design specific interactions to fit certain targets in cancer cells."

They tested candidates for their effects on embryonic zebrafish blood vessels, which behave similarly to human cancer blood vessels. Molecules that blocked blood vessel growth in the fish were found to do the same in mice, and Cheresh hopes they will soon be tested in cancer patients.

The drug screen system has several advantages, Cheresh explained. Most standard screens test 400,000 candidates in test tubes to identify a single drug candidate. His group's screening method requires fewer than 100 compounds to be screened because they are rationally designed, look for specific types of targets, and use a zebrafish model, testing molecules in cells, tissues and organs for "physiological relevance." The zebrafish is a popular drug research model because it is transparent and the effects of drugs are easily monitored.

In addition, he said, the rational design approach provides drugs that are more selective, hitting desired targets and yielding fewer side effects.

Co-authors include: Eric A. Murphy, David J. Shields, Konstatin Stoletov, Michele McElroy, Joshua Greenberg, Jeff Lindquist, Lisette Acevedo, Sudarshan Anand, Bharat Kumar Majeti, Breda Walsh, Michael Bouvet, Richard L. Klemke, Wolfgang Wrasidlo, Moores UCSD Cancer Center; Elena Dneprovskaia, TargeGen, Inc., San Diego; Igor Tsigelny, Adrian Saldanha, UCSD; Robert M. Hoffman, Moores UCSD Cancer Center and Anticancer, Inc., San Diego; Peter K. Vogt, The Scripps Research Institute, La Jolla; Lee Arnold, Kinagen, Inc., Encinitas, CA.

Funding support came from the National Cancer Institute and Kinagen, Inc.

The Moores UCSD Cancer Center is one of the nation's 40 National Cancer Institute-designated Comprehensive Cancer Centers, combining research, clinical care and community outreach to advance the prevention, treatment and cure of cancer.

Steve Benowitz | EurekAlert!
Further information:
http://www.ucsd.edu
http://health.ucsd.edu/cancer

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>