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DURHAM, N.C.-- 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.