Duke, UNC Researchers Target ‘Achilles Heel’ in Brain Tumors

Editor’s note: This article is part of WRAL Local Tech Wire’s efforts to highlight research at universities across the Carolinas and Georgia.

DURHAM - Researchers at Duke University Medical Center and the University of North Carolina, Chapel Hill are exploiting an "Achilles Heel" of brain tumors that may selectively kill tumor cells while sparing surrounding brain tissue.

Although most cancer cells thrive by avoiding the normal process of programmed cell death, or apoptosis, the researchers found a way to turn this normal cell suicide way up for brain cancer cells.

"In collaboration with Dr. Deshmukh's lab at UNC, we attempted to come up with a way to specifically target tumor cells without damaging surrounding cells," said Sally Kornbluth, Ph.D., Professor of Pharmacology and Cell Biology and Vice Dean of Basic Sciences.

In addition to turning off normal cell death, brain cancers, such as glioblastomas and medulloblastomas, are generally resistant to traditional chemotherapy. And chemotherapy and radiation can also lead to significant neurological defects because they kill both cancerous and healthy brain.

In their study, published in the December issue of the Proceedings of the National Academy of Sciences, the researchers found that brain tumor cells are particularly sensitive to a protein called cytochrome c, which is involved in programmed cell death.

Because of this difference, lab-cultured, human brain tumor cells treated with cytochrome c were killed, while mature neurons were not affected.

"This work highlights a previously unappreciated vulnerability within tumor cells. It also suggests a powerful technique by which new chemotherapeutic agents could act," Kornbluth said.

"Apoptosis could be induced within brain tumors by small molecules that mimic cytochrome c," said Mohanish Deshmukh of UNC, co-senior
author of the study.

All types of brain tumors appear to share this vulnerability, Kornbluth said.
The next step toward a real-world treatment would be to determine how to deliver cytochrome c directly to brain cells without affecting other cells in the body. Indeed, much of conventional chemotherapy's more debilitating side effects, including extreme fatigue and low blood-cell counts, come from the inadvertent elimination of healthy cells.

The study was supported by grants from the National Institutes of Health and the Pediatric Brain Tumor Foundation.