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Scientist works to improve treatment for brain tumors

With a five-year, $1 million grant from the National Cancer Institute, a Wake Forest University Baptist Medical Center researcher will work to improve the effectiveness of a drug that he developed for the most deadly type of brain tumor.

Waldemar Debinski, M.D., Ph.D., pioneered a method to destroy cells of glioblastoma multiforme (GBM) with less damage to healthy cells. The drug is currently being tested in clinical trials and Debinski is working on its fourth generation in the laboratory.

With the grant, Debinski will work to identify the best way to deliver the drugs to cancer cells for maximum effectiveness.

"Our goal is to prolong survival in these patients ?that's what we are fighting for," he said.

Currently, people with GBM have a median survival time of 12 to 14 months and a five-year survival rate of 1 percent to 5 percent.

The drug's development was based on Debinski's finding that glioblastoma cells over-express large amounts of a receptor for interleukin 13 (IL13), a protein that regulates the immune system. Debinski combined IL13 with a bacterial toxin to create a cytotoxin drug to target cancer cells and less healthy cells. The efficacy of the first generation of the drug has been has been tested in a clinical trial (phase III) involving 190 patients at 40 different medical centers worldwide. The results are expected later this year.

Since the development of the original drug, Debinski has learned more about the structure of IL13, its receptors, how the cytotoxin binds to it and how the biological properties of tumors may affect it. His goals in the current project are to improve the drug's design so it has better contact with the receptor and to determine the most effective toxin for killing glioblastoma cells, while leaving normal cells unharmed.

"Our aim is to identify the drug design that has the most potent anti-tumor efficacy," he said.

Debinski will also explore how cancer cells ' lack of oxygen affects the treatment. Hypoxia, a lack of oxygen in tissues that causes cell stress, is a characteristic common to all solid tumors and is known to interfere with standard therapies. Researchers aren't sure exactly what causes hypoxia ?one theory is that the blood vessels in tumors are underdeveloped compared to the needs of rapidly proliferating cells.

They also aren't sure how it affects treatment using cytotoxins. Do the hypoxic regions of a tumor need more or less drug treatment? Debinski, in collaboration with the laboratory of Costas Koumenis, Ph.D., will explore that question with the goal of identifying which area of the tumor to focus on to achieve maximum results. The drug is delivered to the tumor through small cathethers, allowing physicians to determine the amount and specific location of treatment.

"With the help of this research grant, we hope to optimize the clinical delivery of the advanced form of the drug," said Debinski.

Debinski directs the Wake Forest Brain Tumor Center of Excellence. The goal of the center, which was formed in 2003, is to find better treatments ?and one day a cure ?for malignant brain tumors. In addition to its focus on research, the center provides a comprehensive program for patient care, and is the first center in the state to offer Gamma Knife stereotactic radiosurgery, a knifeless approach to brain surgery and radiation therapy.


Source:Wake Forest University Baptist Medical Center

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