Researchers at Wake Forest University Baptist Medical Center have identified a second promising treatment target for glioblastoma multiforme, one of the most deadly types of brain tumors. The research results are reported in the October issue of Molecular Cancer Research.
"We've found that a particular protein may play a major role in the progression of these tumors, suggesting an attractive new treatment approach," said Waldemar Debinski, M.D., Ph.D., director of the Brain Tumor Center of Excellence at Wake Forest University Baptist Medical Center.
This was the first study to investigate the presence and significance of a protein called EphA2 in brain cancer cells. This protein, which is found in cell membranes, allows normal cells to communicate with their environment and each other. In its normal active state, the protein seems to inhibit abnormal cell growth and division.
Debinski and colleagues demonstrated that glioblastoma cells have significantly increased levels of the protein EphA2 compared to normal cells – but it is in an inactive form. They believe that this inactive form of EphA2 aids in the survival and spread of cancer cells.
To test their hypothesis, they treated glioblastoma cells with ephrinA1, a naturally occurring molecule that binds to EphA2 and activates it. They had already demonstrated that ephrinA1 is present at much lower levels in cells and tumors with increased levels of inactive EphA2.
"We observed that cells treated with ephrinA1 slowed down their growth and were less likely to exhibit invasive properties," said Debinski.
The researchers believe that developing medication to change levels of EphA2 and ephrinA1 offers new promise for successfully treating glioblastoma multiforme, which is the most common form of brain tumor and the least curable of all human cancers. The majority of the 17,500 brain tumors diagnosed each year in the United States are glioblastomas. Patients have a median survival time of nine to 12 months and a five-year survival rate of 1 to 5 percent.
"EphA2 represents a novel target for the development of molecular therapeutics for the imaging and treatment of patients with glioblastoma," said Debinski. "New therapies are clearly needed because, despite the standard treatment of surgically removing the tumor and treating the patient with chemotherapy and radiation, survival has increased only slightly over the past 30 years."