Navigation Links
New strategy likely to speed drug development for rare cancers
Date:9/15/2011

Researchers have identified promising new therapies for ependymoma, a rare tumor with few treatment options. St. Jude Children's Research Hospital investigators led the effort, which used a new, faster drug development system that combines the latest drug screening technology with the first accurate animal model of the tumor.

Investigators identified several dozen new and existing drugs as possible ependymoma treatment candidates. The drugs were found by screening 5,303 existing medicines, natural products and other compounds for activity against the tumor, which develops in the brain and spine of children and adults. The work is published in the current edition of the scientific journal Cancer Cell.

The list of candidate drugs included 5-fluorouracil (5-FU). 5-FU has been widely used to treat a variety of adult cancers but has not been formally tested against ependymoma. Based on study results, St. Jude is planning a clinical trial of 5-FU in young ependymoma patients, said senior author Richard Gilbertson, M.D., Ph.D., director of the St. Jude Comprehensive Cancer Center. Gilbertson credited the method used in this study with highlighting 5-FU's potential.

Researchers hope to use the same system to expand chemotherapy options for patients with other cancers. "This approach should significantly advance the efficiency and speed with which we discover and develop new treatments for rare cancers and cancer subtypes," the investigators noted. Jennifer Atkinson, Ph.D., a former St. Jude postdoctoral fellow, is the first author. R. Kiplin Guy, Ph.D., chair of the St. Jude Department of Chemical Biology and Therapeutics, and Gilbertson are corresponding authors.

Rather than waiting years for clinical trial results, this system promises to take just months to provide key information about a drug's effectiveness and optimal administration, Gilbertson said.

The results are good news for patients with ependymoma and other cancers where treatment options are limited and the outlook remains bleak. While overall childhood cancer survival rates are now almost 80 percent, ependymoma remains incurable in up to 40 percent of patients. The tumor is found in 150 to 200 U.S. children annually, making it the third most common pediatric brain tumor. Treatment has changed little in the past 40 years and is limited to surgery and radiation.

Along with identifying and prioritizing drug development candidates against ependymoma, the research provided insight into the tumor's biology. The screening identified several messenger proteins, known as kinases, as possible new regulators of the tumor cell proliferation that makes cancer deadly. The abnormal tumor kinase activity occurred in certain pathways in tumor cells, including the insulin-signaling pathway and the centrosome cycle.

This study builds on earlier research led by Gilbertson that showed ependymoma includes nine different tumor subtypes. Each begins when particular mutations occur in stem cells from different regions of the brain or spine. Stem cells are the specialized cells that can divide and take on more specific functions.

For this project, investigators focused on a subtype D ependymoma. In earlier research, Gilbertson and his colleagues showed that extra copies of the EPHB2 gene caused this tumor subtype. The investigators used this information to develop an accurate model of subtype D ependymomas in mice. The mouse model includes the same mutation in the same neural stem cell responsible for the human disease and was crucial for speeding drug development.

Researchers used an automated system to check 5,303 existing drugs, natural products and other compounds for activity against four different types of mouse brain cells, including normal neural stem cells, subtype D ependymoma tumor cells and cells from a different brain tumor.

Of the 634 compounds that showed activity against subtype D ependymoma cells, four demonstrated a two-fold greater ability to block the growth of the tumor cells, but not normal cells. The drugs included 5-FU and two closely related compounds. The fourth was beta-escin, which belongs to a family of drugs that are generating interest as potential chemotherapy agents.

5-FU also proved more effective than four other chemotherapy drugs in slowing tumor growth and extending the lives of mice with subtype D ependymoma. 5-FU also appeared less toxic to normal mouse brain cells than another drug, bortezomib, included in the study. The findings provided preliminary evidence that the screening system might provide an early indication of drug toxicity. The information could help guide treatment and prioritize drugs for development, researchers said.

The screening also highlighted a possible role for kinase inhibitors. Those are drugs that block activity of proteins that help drive cell division and sustain tumors. More than 18 inhibitors are in clinical trials that target the kinases this study tied to proliferation of both normal and ependymoma tumor cells.


'/>"/>

Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

Related medicine news :

1. Study points to strategy for overcoming resistance to targeted cancer drug
2. Research identifies marketing mix strategy for pharmaceutical firms
3. New Strategy Trains All Soldiers in Trauma Care
4. NIH supports new research strategy for finding a cure for HIV
5. Coping Strategy Depends on Strength of Emotion: Study
6. Innovative duct tape strategy saves hospitals time, money; improves infection prevention
7. New strategy to attack tumor-feeding blood vessels
8. Researchers develop strategy to improve patient adherence
9. Potential new strategy to reduce catheter blockage
10. A Pacman strategy to boost the immune system to fight cancer
11. Scientists devise targeted therapy strategy for rare form of childhood cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/27/2017)... (PRWEB) , ... February 27, 2017 , ... The threat ... went to work for a company involved in the underground testing of nuclear weapons. ... “Dying for Answers: Expendable Workers of the Cold War Nuclear Testing,” Clayton exposes the ...
(Date:2/27/2017)... ... February 27, 2017 , ... ... on laser diffraction analysis as a tool to characterize particle size distributions in ... to obtain improved results and novel scientific findings. It describes methods of optimized ...
(Date:2/27/2017)... ... February 27, 2017 , ... Texas based retail electric company ... Power's RCE (Residential Customer Equivalent) count exceeds 150,000. , Discount Power ... customers and 2,250 RCEs at the time of acquisition. In the three years ...
(Date:2/27/2017)... Francisco, CA (PRWEB) , ... February 27, 2017 ... ... clinic serving San Francisco and environs, is proud to announce an upgrade to ... information on the upgraded Yelp page on topics as diverse as Platelet Rich ...
(Date:2/26/2017)... ... February 26, 2017 , ... Today, ... the 7th Edition of International Social Design Awards. , The 7th A' ... System Designers, Governments and Institutions worldwide with realized projects and conceptual works. , ...
Breaking Medicine News(10 mins):
(Date:2/27/2017)... Feb. 27, 2017   Royal Philips ... global leader in health technology, today announced 510(k) ... (FDA) to market its ElastQ Imaging capability, further ... ultrasound systems. ElastQ Imaging enables simultaneous imaging of ... essential for the diagnosis of various liver conditions. ...
(Date:2/27/2017)... , Feb. 27, 2017  Infinity Pharmaceuticals, Inc. ... the Cowen and Company 37 th Annual Healthcare ... ET in Boston, MA. A ... the Investors/Media section of Infinity,s website at www.infi.com ... the event. About Infinity,Infinity is an innovative ...
(Date:2/27/2017)... 27, 2017 A recent research report published ... market alone is expected to reach a value of $55.8 billion ... along with 28 states have legalized marijuana for medical uses. In ... Florida , North Dakota , ... to use the drug in medical applications such as chemotherapies and ...
Breaking Medicine Technology: