Scientists zero in on three-drug cocktail crystal ball against brain tumors

January 1st, 2008 - 4:56 pm ICT by admin  

Washington , Jan 1 (ANI): Researchers at the Wake Forest University Baptist Medical Center have proposed a suited-to-all, three-drug cocktail treatment for a type of brain tumor called glioblastoma multiforme (GBM).

Though the prognosis of this type of tumor is difficult, two drugs out of the three have already been developed and work for developing the third is underway.

The researchers said that the drugs, which selectively target and kill cancer cells while sparing the healthy brain, could be tested in patients within 5 years.

The study was led by Waldemar Debinski, M.D., Ph.D., senior researcher and director of the Wake Forest Brain Tumor Center of Excellence.

The first-ever documented “molecular signature” of GBM tumors would rule the treatment. This research comes in line with an early research indicating the presence of three different proteins found in high levels individually in these cancers.

During the current study, 76 specimens of brain tumor were examined, including 46 GBMs, and nine normal brain samples, in order to find out the frequency of appearance of these markers together.

The study indicated that the expression of all three markers was considerably higher in GBM tissue in comparison to normal brain and to brain tumors less aggressive than GBM.

The main highlight was that all GBM tumors had at least one of the markers present and almost 95 percent of tumors had at least two.

“This finding offers a unique opportunity for treatment. 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,” said Debinski.

In a recent issue of Molecular Cancer Therapeutics, the researchers reported developing a potent treatment targeted to one of the proteins (EphA2).

Also, a drug targeted to a second protein, interleukin 13 receptor alpha 2, (IL-13RN2),is already being tested alone in a phase 3 clinical trial.

The second protein is showing promising results to patients in the current trial, and newer generations are in development. Researchers are also working to develop a drug to target a third marker (Fra-1).

However, current treatments like chemotherapy and radiation therapy often prove ineffective to GBM tumors.

It was discovered that the three markers were not found in healthy brain tissue, indicating that the proteins are more suited as targets for therapies designed to kill cancer cells and spare healthy brain tissue.

During experimentation, this treatment effectively killed all the over-expressing EphA2 cells within 48 hours. It was also effective at reducing tumors in mice.

The treatment’s potency was then compared to the previous drug developed by Debinski in order to target cells expressing IL-13RN2.

“Both were extremely effective and highly potent. 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,” said Debinski.

He said that the combination treatment also had implications in breast, pancreas and prostate cancers, having high levels of these proteins.

The third marker, Fra-1, supposedly controls the malignant features of brain tumor cells, such as the development new blood vessels to “feed” the tumor.

Another advantage to target the three proteins is that the drug cocktail affects targets existing in the GBM cellular signaling pathways, including a pathway (epidermal growth factor receptor vIII) that controls the expression of all three proteins. These pathways are considered vital in progression of tumor.

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

The study is reported in the recent issue of Clinical Cancer Research. (ANI)

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