Featured Research

from universities, journals, and other organizations

Drug created to keep tumor growth switched off

Date:
February 14, 2010
Source:
University of California - San Diego
Summary:
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 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.

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, PDGFRβ and B-RAF -- both of which are found to be activated in tumors and in blood vessels that feed tumors. Since PDGFRβ 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.


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University of California - San Diego. "Drug created to keep tumor growth switched off." ScienceDaily. ScienceDaily, 14 February 2010. <www.sciencedaily.com/releases/2010/02/100211175217.htm>.
University of California - San Diego. (2010, February 14). Drug created to keep tumor growth switched off. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2010/02/100211175217.htm
University of California - San Diego. "Drug created to keep tumor growth switched off." ScienceDaily. www.sciencedaily.com/releases/2010/02/100211175217.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
Hagel Gets Preview of New High-Tech Projects

Hagel Gets Preview of New High-Tech Projects

AP (Apr. 22, 2014) Defense Secretary Chuck Hagel is given hands-on demonstrations Tuesday of some of the newest research from DARPA _ the military's Defense Advanced Research Projects Agency program. (April 22) Video provided by AP
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins