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 b
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Wake Forest University Baptist Medical Center