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Researcher discovers new weapon to treat brain cancer cells resistant to chemotherapy

Patients diagnosed with the most common and most deadly type of brain tumor have few options. Even the most aggressive surgery to remove the glioblastoma multiforme tumor mass leaves microscopic residual tumor cells behind that migrate to another part of the brain and grow again.

Dr. William Maltese, professor and chair of biochemistry and cancer biology, prepared a new drug formulation to induce cell death in glioblastoma.

Oncologists need a new way to treat this invasive and fast-growing tumor, which doesn’t respond to radiation or chemotherapy, and a University of Toledo researcher might have found it.

Dr. William Maltese, professor and chair of the UT Department of Biochemistry and Cancer Biology in the College of Medicine and Life Sciences, has discovered a new way to kill cells; he cslls it methuosis, which is from the Greek for “to drink to intoxication.” Rather than the common cell death method of apoptosis, which can be triggered with radiation and drugs that cause DNA damage, prompting the cell to shrink and disintegrate, this new form of cell death causes the cell to take on liquid until it explodes.

“The average survival rate for adults diagnosed with this type of tumor is only about one and one-half years. Next to pancreatic cancer, this is the most deadly type of cancer, and the current treatments we have are ineffective,” Maltese said. “We need to be aggressive in our research to achieve a breakthrough. There are treatments for other types of cancer that we certainly can improve upon, but we need to make it a priority to find something that works for these patients who now have very few options.”

Unlike apoptosis, this new methuosis cell death pathway does not occur naturally. But Maltese and his research team have found an appropriate drug-like molecule to induce it. A patent application is in process on the compound.

Early lab tests show that methuosis is effective in destroying glioblastoma multiforme cells that have become resistant to the front-line drug, temozolomide, but more research needs to be done to determine if molecules that induce this form of cell death might be useful for treating cancer patients.

Maltese recently received a $1.4 million grant from the National Institutes of Health to continue his research. The next step is to find the best way to target the molecule to only induce the cell death in tumor cells and not normal cells. Biomarker research aimed at identifying the specific tumor proteins that are targeted by the death-inducing molecule will help to achieve this goal, Maltese said.

The UT research team also will investigate the most effective way to treat the tumor, which could include local delivery at the surgery site when the tumor is removed or with a specific drug formula that can be given intravenously and is able to get through the blood-brain barrier.

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