Promising new molecular targets and treatment approaches for some of the most malignant brain tumors

May 8 2005

Researchers at Wake Forest University Baptist Medical Center have found promising new molecular targets and treatment approaches for some of the most malignant brain tumors.

Results of three separate studies were presented at the World Federation of NeuroOncology meeting and the European Association for NeuroOncology meeting, both in Edinburgh, Scotland, on May 6 and 7.

The research involved glioblastoma multiforme, the most common form of brain tumor and the least curable of all human cancers.

The first study identified a protein that seems to control the malignant features of brain tumor cells, suggesting a new treatment target for anti-cancer drugs. Researchers found that a little-known protein called Fra-1 was effective in controlling vascular endothelial growth factor D, a factor that promotes the growth of new blood vessels in most malignant brain tumors.

"This protein seems to be important in how tumors grow and how they may spread to healthy tissue," said Waldemar Debinski, M.D., Ph.D., director of the Brain Tumor Center of Excellence at Wake Forest University Baptist Medical Center. "It is a very powerful biological factor and may be an attractive target for anti-cancer therapy."

The second study builds in earlier research by Debinski and colleagues that found that glioblastoma cells have a particular type of receptor for interleukin 13 (IL-13), a naturally occurring protein that regulates the immune system in the body. Normal cells do not have these same receptors. IL-13 is a very attractive target for molecular anti-brain tumor therapies and two clinical trials are currently ongoing.

The new study examined the role of proteins called cytokines in augmenting the amount of IL-13 receptor expressed by tumor cells. The use of these cytokines may improve treatment of glioblastoma cells by increasing the levels of IL-13 receptor in brain tumors and thus making them more accessible to drugs targeting the receptor.

The third research study focused on the search for novel specific molecular markers or targets in brain tumors. EphA2, a cell membrane-anchored protein-receptor, was shown to be uniformly overexpressed in malignant brain tumors, but not in normal brain tissue.

"EphA2 represents a novel target for the development of molecular therapeutics for the imaging and treatment of patients with glioblastoma," said Debinski.

Denise Gibo, B.S., Jill Wykosky, B.S., and Nianping Hu, Ph.D., from Debinski's laboratory contributed to this work.