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Trial Drugs Offer Hope for Brain Cancer

Cocktail could target specific proteins in tumors

THURSDAY, Nov. 20, 2003 (HealthDayNews) -- By targeting specific small proteins in cancerous brain tumors, researchers hope to develop potent new treatments.

Initial results of these experimental drugs in mice and human cancer cells appear dramatically successful, according to a presentation made Nov. 19 at the Molecular Targets and Cancer Therapeutics meeting in Boston.

"We have targeted ways cancer cells stimulate tumor growth, promote their survival and create new blood vessels," says lead researcher Dr. Jeremy Rich, an assistant professor of medicine in the Brain Tumor Center at Duke University.

In his presentation, Rich discussed three approaches to treatments. "One is a drug called ZD6474, which is directed at vascular endothelial growth factor (VEGF), which promotes blood vessel growth," Rich says. However, this drug also blocks epidermal growth factor (EGF), which is involved in new blood vessel growth, he adds.

What is unusual about this drug is that it blocks both VEGF and EGF, whereas most drugs block only one or the other, Rich notes. "In clinical trials, neither single blocker has worked great," he says.

"But the combination has worked fantastically well," Rich notes. "This combination has worked against gliomas, the most common type of brain tumor, but also other types of tumors. . . That's a pretty exciting finding."

SB431542, another new compound, was tested in human malignant glioma cell lines. The drug successfully blocked the receptor protein called transforming growth factor-beta (TGF-beta).

Blocking the activity of the TGF-beta receptor also blocked the protein PAI-1. This protein, which normally communicates with TGF-beta in cancer cells, is a predictor of poor prognosis in patients.

Another drug combination, AEE788 and RAD001, blocked the growth of glioblastomas. AEE788 targets epidermal growth factor receptor (EGFR) and also VEGF.

RAD001 targets mTOR. This protein is needed to regulate cell metabolism. Without it, cells cannot grow properly. Combining these drugs blocked tumor growth more effectively than either drug alone.

"These developments will enable us to develop a cocktail approach to treating each patient," Rich says. "We can tailor for each patient the particular needs the patient has, based on the type of tumor."

Rich sees future treatment of brain cancers, and other cancers, as using a combination of these drugs, customized for each patient, plus chemotherapy and radiation. Rich believes that eventually drug therapy alone may prove effective, eliminating the serious side effects associated with chemotherapy and radiation.

"There is really hope for the future, because treatments are changing rapidly. There are a lot of new treatments that are showing promise and that we hope will lessen side effects and increase our ability to control cancers," Rich says.

Dr. Mitchel Berger, a professor of neurosurgery and chairman of the Department Neurological Surgery at the University of California at San Francisco, comments, "At the UCSF Brain Tumor Research Center, we are conducting very similar trials with similar small molecule inhibitors that do basically the same thing, that is block EGFR, VEGF, mTOR, etc."

"We are all optimistic, but must remain cautious, since it is a long reach from animal models to humans. Notwithstanding, many of us committed to brain tumor research and new treatment therapies believe that we are making significant progress with these small molecule inhibitors," he adds.

More information

To learn more about brain tumors, visit the National Brain Tumor Foundation or the National Cancer Institute.

SOURCES: Jeremy Rich, M.D., assistant professor, medicine, Brain Tumor Center, Duke University, Durham, N.C.; Mitchel Berger, M.D., professor, neurosurgery, and chairman, Department Neurological Surgery, University of California, San Francisco; Nov. 19, 2003, presentation, Molecular Targets and Cancer Therapeutics meeting, Boston
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