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Neuro Innovations - Turning the Tables on Brain Tumors

Collaborations in Discovery

Turning the Tables on Brain Tumors

Date: November 1, 2011

There’s a particular urgency to the quest to find a drug effective against the brain tumors called glioblastomas. Because they’re a form of cancer that spreads quickly through the brain, surgery and radiation usually can’t get at all the cancerous cells. “We need more creative ways of fighting this disease,” says Gregory Riggins, a cancer researcher in the neurosurgery department of Johns
Hopkins. Riggins is unleashing more than his share of creativity in the battle, helping to come up with an unexpected and promising strategy for a drug that could wipe out glioblastoma cells while leaving normal brain cells unscathed.

The first important clues to the strategy came when Riggins and others collaborated about five years ago with renowned Johns Hopkins researcher Bert Vogelstein to try to identify which genes in a cell could be linked to glioblastomas. They discovered that mutations in a gene called  IDH1 seemed to play a role in the tumor’s formation. But what did the gene do?

A crucial insight came from another Riggins collaborator, cancer researcher Chi Dang. Dang suspected that IDH1 was producing an enzyme that was using up one of the key molecules needed for a cell’s metabolism, forcing the glioblastoma cell to rely on a different enzyme to get the energy it needed. Riggins and his collaborators saw that as a vulnerability they might be able to exploit. “Cancer cells usually alter themselves to gain an advantage over other cells,” he explains. “Now we saw we might have a chance
to turn the tables on them.”

If they could find a drug that interfered with the enzyme that only glioblastoma cells depend on for energy, then those cells would essentially starve, while normal cells continue to produce energy. Riggins and his collaborators soon found a compound that seemed to do the trick. Unfortunately, the compound doesn’t make for a good drug because of difficulties in getting it into the brain and into cells. So Riggins’ group is working furiously to tweak the compound to make it a better drug candidate, as well as to find more suitable compounds that can perform similarly.

“It’s all part of the long process of developing a new drug,” says Riggins. “But at least now we have an approach for selectively targeting glioblastoma cells, and that’s a huge first step.”

  • Challenge: Starve brain-tumor cells without hurting other cells
  • Approach: Block an enzyme that only glioblastomas rely on for energy
  • Progress: Work is focusing on modifying a blocker to get it past the blood-brain barrier
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