Navigation Links
Research suggests new treatment suitable for all patients
Date:12/31/2007

WINSTON-SALEM, N.C. -- New research at Wake Forest University Baptist Medical Center suggests that a three-drug cocktail may one day improve outcomes in patients with glioblastoma multiforme (GBM), a type of brain tumor with a dismal prognosis. Two of the drug candidates have been developed, and the team is working on the third -- all targeted to kill or impair cancer cells and spare healthy brain.

Waldemar Debinski, M.D., Ph.D., senior researcher and director of the Wake Forest Brain Tumor Center of Excellence, predicts that the cocktail could be tested in patients within five years.

The treatment would be based on the first-ever documented "molecular signature" of GBM tumors. The researchers had previously reported that three different proteins are found in high levels individually in these cancers. In the current study, reported in Clinical Cancer Research, they examined 76 specimens of brain tumor, including 46 GBMs, and nine normal brain samples, to determine how frequently the markers appeared together.

Expression of all three markers was significantly higher in GBM tissue compared to normal brain and to brain tumors that aren't as aggressive as GBM. Particularly important was that all GBM tumors had at least one of the markers present and 95 percent of tumors had at least two.

"This finding offers a unique opportunity for treatment," said Debinski. "Without any pre-therapy testing, we would know for sure that at least one of these targets is highly present in each patient and that the patient is suitable for the combination of off-the-shelf drugs. It is like having a crystal ball."

In a recent issue of Molecular Cancer Therapeutics, the researchers reported developing a potent treatment targeted to one of the proteins (EphA2). In addition, a drug targeted to a second protein, interleukin 13 receptor alpha 2 (IL-13R2), is already being tested alone in a phase 3 clinical trial. In this trial, the second protein is showing significant benefits to patients, and newer generations are in development. The team is working to develop a drug to target a third marker (Fra-1).

GBM tumors are often resistant to current treatments, including chemotherapy and radiation therapy. The mean survival rate of patients with GBM is about 14 months and has improved only slightly over the past decades.

"Developing molecularly targeted therapies using genetically engineered bacterial toxins represents an attractive option that may improve outcomes," said Debinski.

The fact that the three markers were not found in healthy brain tissue suggests that the proteins are highly suited as targets for therapies designed to kill cancer cells and spare healthy brain tissue. In Molecular Cancer Therapeutics, the team reported success creating a drug to kill cancer cells that have high levels of EphA2. The drug, which would be delivered by catheters directly to the tumor, was created by chemically linking a protein that binds to EphA2 with a modified bacterial toxin.

In the laboratory, the treatment potently killed all of the over-expressing EphA2 cells within 48 hours. It was also effective at reducing tumors in mice. The researchers compared the treatment's potency to the drug Debinski had previously developed to target cells that express IL-13R2.

"Both were extremely effective and highly potent," said Debinski. "Some of the tumor cells responded to the IL-13 cytotoxin, some responded to EphA2-targeted cytotoxin and some responded to both. This illustrates why we need a cocktail to cover as many patients as possible."

He said this combination treatment might also apply to breast, pancreas and prostate cancers, which also have high levels of these proteins.

The third marker, Fra-1, is believed to control the malignant features of brain tumor cells, such as the development new blood vessels to "feed" the tumor.

An additional benefit of targeting the three proteins is that the drug cocktail affects targets residing in the GBM cellular signaling pathways, including a pathway (epidermal growth factor receptor vIII) that is known to control the expression of all three proteins. These pathways are known to be important in tumor progression.

"With the drug cocktail we may be taking care of cancer cells that are really important for tumor survival," said Debinski. "It may be the best of two worlds."


'/>"/>

Contact: Shannon Koontz
shkoontz@wfubmc.edu
336-716-2415
Wake Forest University Baptist Medical Center
Source:Eurekalert

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. Children of depressed moms do better when dad is involved, SLU researcher finds
3. UCLA researchers identify markers that may predict diabetes in still-healthy people
4. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
5. New research shows how chronic stress worsens neurodegenerative disease course
6. New research explores newborn in-hospital weight loss
7. Research may unlock mystery of autisms origin in the brain
8. Bipolar disorder relapses halved by Melbourne researchers
9. HIVs impact in Zimbabwe explored in new research
10. U.S. Research Funding Continues to Flatten as U.S. Health Costs Climb - in August 31 Science
11. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/6/2016)... ... May 06, 2016 , ... ... TX has announced the latest beneficiary of their ongoing community enrichment program. The ... childhood leukemia. Young Mason McGaughey faces many more months of treatments, leaving his ...
(Date:5/6/2016)... ... 06, 2016 , ... The joy associated with Mother’s Day is mixed with worry and fear ... units (NICUs) across the country. For the first time ever, the March of Dimes ... who spend their Mother’s Day beside a crib surrounded by lifesaving equipment or peering through ...
(Date:5/6/2016)... ... May 06, 2016 , ... A wide variety of national pet product manufacturers, companies and brands ... Media Showcase Wednesday, May 18 from noon to 8 p.m. at New York City’s Roger ... new and established home, garden, outdoor and safety pet products in today’s marketplace. ...
(Date:5/6/2016)... ... May 06, 2016 , ... Fat-Freezing, which is what ... body, is the most popular among body sculpting options, according to a new ... cosmetic surgeon Dr. Richard Buckley, medical director of MilfordMD Cosmetic Dermatology Surgery & ...
(Date:5/6/2016)... ... May 06, 2016 , ... From May 4 to 6, ... members the unique opportunity to learn more about Signia’s technology and the successful business ... “It is our priority to see practices succeed in this highly competitive industry,” said ...
Breaking Medicine News(10 mins):
(Date:5/5/2016)... , May 5, 2016 ... addition of the  "Europe Systemic Lupus Erythematosus ...  report to their offering.       ... The latest research Europe Systemic Lupus Erythematosus ... provides comprehensive insights into Systemic Lupus Erythematosus ...
(Date:5/4/2016)... COUNTY, Calif. , May 4, 2016  It,s time for an upgrade. There ... shown on a brilliant 3.5 inch LCD, the illustrious DVMAXX HD  offers unparalleled ... brands as well as a world class manufacturer of innovative technology.  Photo ... ... ...
(Date:5/4/2016)... , May 4, 2016 ... Jerusalem announced today that it had signed an ... Inc. , developer of novel protein degradation and immunomodulatory ... and commercialization of drug candidates representing first-in-class therapy for ... were not disclosed. The novel technology was ...
Breaking Medicine Technology: